Conference Agenda

Mitochondrial disease: past successes and future challenges

Doug Turnbull

Newcastle University, United Kingdom

The role of mtDNA variation in common and rare diseases

Patrick F. Chinnery

Cambridge-UK, United Kingdom

How mtDNA can talk with the complex landscape of nuclear encoded OXPHOS information?

José Antonio Enriquez

Spanish National Center for Cardiovascular Research (CNIC)

Understanding the pathophysiological mechanisms of mitochondrial diseases with MITOMICS through an integrated multi-OMICS approach of Mitomatcher, the French mitochondrial disease database

Sylvie Bannwarth¹, Alexandrina Bodrug², Céline Bris², MitoDiag Network³, Stéphane Tirard⁴, Silvia Bottini⁵, Marie Deprez⁷, Magalie Barth², Patrizia Bonneau², Pascal Reynier², Dominique Bonneau², Justine Labory⁵, Cécile Rouzier¹, Annabelle Chaussenot¹, Samira Ait-El-Mkadem-Saadi¹, Shahram Attarian⁶, Marco Lorenzi⁷, Véronique Paquis-Flucklinger¹, Anthony Brooks⁸, Vincent Procaccio²

1: Université Côte d’Azur, INSERM U1081, CNRS UMR7284, IRCAN, CHU de Nice, Nice, France; 2: Département de Génétique, UMR CNRS 6015 INSERM 1083, CHU et Université d’Angers, Angers, France; 3: Réseau français des laboratoires de diagnostic pour les maladies mitochondriales (Bordeaux, Caen, Grenoble, Lille, Lyon, Le Kremlin-Bicêtre, Pitié Salpêtrière, Necker Enfants Malades, Reims), Centres de référence pour les maladies mitochondriales (CALISSON, CARAMMEL), France; 4: Université de Nantes, Nantes, France; 5: Université Côte d’Azur, MDLab, Nice, France; 6: Filière FILNEMUS, CHU La Timone, Marseille, France; 7: INRIA, Equipe EPIONE, Nice, France; 8: University of Leicester, Dept.Genetics, UK

Generating a complete human panmitogenome

Giulio Formenti¹, Alessandro Achilli², Hansi Weissensteiner³, Anna Olivieri², Andrea Guarracino⁴, Walther Parson^5,8, Nicola Rambaldi Migliore², Martin Bodner³, Valerio Carelli⁶, Leonardo Caporali⁶, Claudio Fiorini⁷, Danara Ormanbekova⁷, Erik Garrison⁴, Nicole Huber³

1: The Rockefeller University, United States of America; 2: Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy; 3: Medical University of Innsbruck, 6020 Innsbruck, Austria; 4: Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA; 5: Medical University of Innsbruck, 6020 Innsbruck, Austria; 6: Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40139 Bologna, Italy; 7: IRCCS Institute of Neurological Sciences of Bologna; 8: Forensic Science Program, The Pennsylvania State University, University Park, PA, USA

Negative selection of mitochondrial DNA mutations in the blood

Imogen Grace Franklin^1,5, Paul Milne^2,5, Jordan Childs¹, Isabel Barrow^1,3, Róisín M Boggan¹, Andrew M Schaefer^1,3, Catherine Feeney^1,3, Rhys H Thomas^1,3, Gráinne S Gorman^1,3, Conor Lawless¹, Yi Shiau Ng^1,3, Matthew Collin^2,4, Oliver M Russell^1,4, Sarah J Pickett^1,4

1: Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne; 2: The Human Dendritic Cell Lab, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne; 3: NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne; 4: Equal Contributions; 5: Equal Contributions

Parsing universal heteroplasmy in a large maternal lineage carrying the common LHON variant m.11778G>A/MT-ND4

Danara Ormanbekova¹, Claudio Fiorini¹, Leonardo Caporali², Alberto Pasti¹, Chiara Giannuzzi², Francesco Musacchia³, Diego Vozzi³, Milton N Moraes-Filho⁴, Solange R Salomao⁵, Adriana Berezovsky⁵, Alfredo A Sadun⁶, Stefano Gustincich³, Patrick F Chinnery⁷, Valerio Carelli^1,2

1: Azienda USL di Bologna - IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 2: Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 3: Istituto Italiano di Tecnologia – IIT, Genova, Italy; 4: Instituto de Olhos de Colatina, Colatina, Espírito Santo, Brazil; 5: Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; 6: Doheny Eye Institute, Los Angeles, CA, USA; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 7: Medical Research Council Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

PNPLA3, MBOAT7 and TM6SF2 modify mitochondrial dynamics in NAFLD patients: dissecting the role of cell-free circulating mtDNA and copy number

Miriam Longo¹, Erika Paolini^1,2, Marica Meroni¹, Michela Ripolone¹, Laura Napoli¹, Giada Tria¹, Marco Maggioni¹, Maurizio Maggio¹, Anna Ludovica Fracanzani^1,3, Paola Dongiovanni¹

1: Fondazione IRCCS Cà Granda Ospedale Policlinico, Italy; 2: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 3: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Italy

Initiation of mitochondrial DNA replication in mammalian cells.

Maria Falkenberg

Gothenburg University, Sweden

Regulation of mitochondrial gene expression in disease

Aleksandra Filipovska

University of Western Australia, Australia

Mitochondrial translation termination at non-canonical stop codons

Annika Krüger¹, Cristina Remes², Dmitrii Igorevich Shiriaev¹, Yong Liu¹, Henrik Spåhr¹, Rolf Wibom¹, Ilian Atanassov³, Minh Duc Nguyen¹, Barry S. Cooperman², Joanna Rorbach^1,3

1: Karolinska Institutet, Stockholm, Sweden; 2: University of Pennsylvania, Pennsylvania, USA; 3: Max-Planck-Institute for Biology of Ageing, Cologne, Germany

Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability

Direnis Erdinc¹, Alejandro Rodríguez-Luis^2,3, Mahmoud R. Fassad^2,4, Sarah Mackenzie⁵, Christopher M. Watson^6,7, Sebastian Valenzuela¹, Xie Xie¹, Katja E. Menger^2,3, Kate Sergeant⁸, Kate Craig^2,9, Sila Hopton^2,9, Gavin Falkous^2,9, Joanna Poulton¹⁰, Hector Garcia-Moreno¹¹, Paola Giunti¹¹, Carlos A. de Moura Aschoff¹², Jonas A. Morales Saute^12,13,14, Amelia J. Kirby¹⁵, Camilo Toro¹⁶, Lynne Wolfe¹⁶, Danica Novacic¹⁶, Lior Greenbaum^17,18,19, Aviva Eliyahu^17,19, Ortal Barel²⁰, Yair Anikster^19,21, Robert McFarland^2,4, Gráinne S. Gorman^2,4, Andrew M. Schaefer^2,9, Claes M. Gustafsson^1,22, Robert W. Taylor^2,4,9, Maria Falkenberg¹, Thomas J Nicholls¹

1: Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE-405 30 Gothenburg, Sweden; 2: Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 3: Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 4: Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 5: The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; 6: North East and Yorkshire Genomic Laboratory Hub, Central Lab, St. James's University Hospital, Leeds, UK; 7: Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK; 8: Oxford Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 9: NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK; 10: Nuffield Department of Women’s & Reproductive Health, The Women's Centre, University of Oxford, Oxford, UK; 11: Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; 12: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil; 13: Department of Internal Medicine, Universidade Federal do Rio Grande do Sul - Porto Alegre, Brazil; 14: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul - Porto Alegre, Brazil; 15: Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA; 16: Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA; 17: The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel; 18: The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel; 19: The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 20: Genomics Unit, The Center for Cancer Research, Sheba Medical Center, Israel; 21: Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; 22: Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

The role of replicative exonucleases in mitochondrial DNA replication and degradation

Christian D Gonzalez, Nadee Nissanka, Carlos T Moraes

University of Miami Miller School of Medicine, United States of America

Processing of mitochondrial RNA in health and disease: the role of FASTKD5.

Hana Antonicka¹, James B. Gibson², Eric A. Shoubridge¹

1: The Neuro & McGill University, Montreal, Quebec, Canada; 2: Dell School of Medicine, University of Texas at Austin, Austin, TX, USA

Mechanisms of mtDNA maintenance and segregation in the female germline

Laura Kremer¹, Lyuba Bozhilova^2,3, Diana Rubalcava-Garcia¹, Roberta Filograna¹, Mamta Upadhyay¹, Camilla Koolmeister¹, Patrick Chinnery^2,3, Nils-Göran Larsson¹

1: Karolinska Institutet, Stockholm, Sweden; 2: MRC Mitochondrial Biology Unit, Cambridge, United Kingdom; 3: Department of Clinical Neurosciences, University of Cambridge, United Kingdom

The human Mitochondrial mRNA Structurome reveals Mechanisms of Gene Expression in Physiology and Pathology

Antoni Barrientos¹, Conor Moran¹, Amir Brivanlou², Flavia Fontanesi¹, Silvi Rouskin²

1: University of Miami, United States of America; 2: Harvard Medical School, United States of America

The role of mitochondria in neuromuscular diseases

Rita Horvath

Cambridge-UK, United Kingdom

Innovative approaches for the molecular diagnosis of mitochondrial disorders

Holger Prokisch

Technical University Munich Institute of Human Genetics

Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing

William L Macken^1,2, Micol Falabella¹, Caroline McKittrick¹, Chiara Pizzamiglio^1,2, Rebecca Ellmers³, Kelly Eggleton³, Cathy E. Woodward^2,3, Yogen Patel^2,3, Robyn Labrum^2,3, Genomics England Research Consortium⁹, Rahul Phadke⁴, Mary M. Reilly¹, Catherine DeVille⁵, Anna Sarkozy⁴, Emma Footitt⁶, James Davison^6,7, Shamima Rahman^6,8, Henry Houlden¹, Enrico Bugiardini^1,2, Rosaline Quinlivan^1,2,4, Michael G. Hanna^1,2, Jana Vandrovcova¹, Robert D.S. Pitceathly^1,2

1: Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2: NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; 3: Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK; 4: Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 5: Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 6: Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 7: National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, London, UK; 8: Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK; 9: Genomics England, One Canada Square London, UK

Biallelic variants in MCAT in an infant with lactic acidosis, lipoylation disorder, and early death

Melanie T. Achleitner¹, Maja Hempel^2,3, Konstantinos Tsiakas⁴, René G. Feichtinger¹, Saskia B. Wortmann^1,5, René Santer⁴, Johannes A. Mayr¹

1: University Children's Hospital, Paracelsus Medical University, Salzburg, Austria; 2: Institute of Human Genetics, University Medical Center Eppendorf, Hamburg, Germany; 3: Current address: Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany; 4: Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany; 5: Amalia Children’s Hospital, Radboudumc, Nijmegen, The Netherlands.

Biallelic PTPMT1 variants impair cardiolipin metabolism and cause mitochondrial myopathy and developmental regression

Micol Falabella¹, Chiara Pizzamiglio^1,2, Luis Carlos Tabara³, Ece Sonmezler⁴, Benjamin Munro⁵, William L. Macken^1,2, Shanti Lu¹, Lisa Tilokani³, Padraig J. Flannery^6,7, Nina Patel^7,8, Simon A. S. Pope^7,8, Simon J. R. Heales^7,8, Jana Vandrovcova¹, Henry Houlden¹, Robert W. Taylor⁹, Cathy E. Woodward⁶, Robyn Labrum⁶, Genomics England Research Consortium¹⁰, Semra Hiz¹¹, Maha S. Zaki¹², Efstathia Chronopoulou¹³, Germaine Pierre¹³, Reza Maroofian¹, Michael G. Hanna^1,2, Yavuz Oktay^4,14,15, Rita Horvath⁵, Julien Prudent³, Robert D. S. Pitceathly^1,2

1: Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2: NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; 3: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge UK; 4: Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey; 5: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 6: Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK; 7: Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK; 8: Neurometabolic Unit, The National Hospital for Neurology and Neurosurgery, London, UK; 9: Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children, Newcastle University, Newcastle upon Tyne, UK; 10: Genomics England, London, UK; 11: Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey; 12: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt; 13: Department of Inherited Metabolic Disease, Division of Women's and Children's Services, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 14: Izmir Biomedicine and Genome Center, Izmir, Turkey; 15: Department of Medical Biology, Faculty of Medicine, Dokuz Eylül University, Izmir Turkey

Heterozygous missense variants in NUTF2 (nuclear transport factor 2) gene, mapping at the OPA8 locus, cause Dominant Optic Atrophy

Agnese Macaluso¹, Alessandra Maresca¹, Concetta Valentina Tropeano¹, Maria Antonietta Capristo¹, Flavia Palombo¹, Leonardo Caporali¹, Claudio Fiorini¹, Danara Ormanbekova¹, Chiara La Morgia¹, Piero Barboni^2,3, Cristina Villaverde^4,5, Carmen Ayuso^4,5, Maria Esther Gallardo^6,5, Majida Charif⁷, Sylvie Gerber⁸, Patrizia Amati-Bonneau⁷, Guy Lanaers^7,9, Jean-Michel Rozet⁷, Bernd Wissinger¹⁰, Valerio Carelli^1,11, Valentina Del Dotto¹¹

1: IRCCS - Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica - Bologna (Italy); 2: Studio Oculistico d'Azeglio - Bologna (Italy); 3: Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele - Milano (Italy); 4: Department of Genetics & Genomics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD-UAM) - Madrid (Spain); 5: Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII - Madrid (Spain); 6: Grupo de investigación traslacional con células iPS, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), Madrid, Spain; Centro de Investigación Biomédica en Red (CIBERER) - Madrid (Spain); 7: Université d’Angers, MitoLab team, UMR CNRS 6015 - INSERM U1083, Unité MitoVasc - Angers (France); 8: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, Institute of Genetic Diseases, Imagine and Paris Descartes University - Paris (France); 9: Departments of Biochemistry and Genetics, University Hospital Angers - Angers (France); 10: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany; 11: Depart. of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna - Bologna (Italy)

Southern African paediatric patients with King Denborough syndrome are exclusively associated with an autosomal recessive STAC3 variant: is this a highly prevalent secondary mitochondrial disease in this African population?

Francois Hendrikus van der Westhuizen¹, Maryke Schoonen¹, Michelle Bisschoff¹, Ronel Human², Elsa Lubbe², Malebo Nonyane², Armand Vorster¹, Karin Terburgh¹, Robert McFarland³, Robert Taylor³, Mahmoud Fassad³, Krutik Patel³, Wilson Lindsay⁴, Michael Hanna⁴, Jana Vandrovcova⁴, The ICGNMD Consortium⁵, Izelle Smuts²

1: Human Metabolomics, North-West University, Potchefstroom, South Africa; 2: Department of Paediatrics, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa; 3: Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; 4: Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom; 5: https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/global-contributor-list

AK3, adenylate kinase isozyme 3, is a new gene associated with PEO and multiple mtDNA deletions

Alessia Nasca¹, Andrea Legati¹, Teresa Ciavattini¹, Nadia Zanetti¹, Eleonora Lamantea¹, Javier Ramón², Ramon Martí², Maria Antonietta Maioli³, Costanza Lamperti¹, Holger Prokisch^4,5, Daniele Ghezzi^1,6

1: Fondazione IRCCS Istituto Neurologico Besta, Italy; 2: Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Autonomous University of Barcelona, Barcelona, Spain; 3: Centro Sclerosi Multipla, P.O. Binaghi, ASL Cagliari, Italy; 4: Technical University of Munich, School of Medicine, Institute of Human Genetics, 81675 Munich, Germany; 5: Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Munich, Germany; 6: Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy

Guanylate kinase 1 deficiency: a novel and potentially treatable form of mitochondrial DNA depletion/deletions syndrome

Agustin Hidalgo-Gutierrez¹, Jonathan Shintaku¹, Eliana Barriocanal-Casado¹, Russ Saneto², Javier Ramon^4,7, Gloria Garrabou^4,5, Frederic Tort^3,4, Jose Cesar Milisenda⁶, Laura Gort^3,4, Alba Pesini¹, Saba Tadesse¹, Mary-Claire King⁸, Ramon Marti^4,7, Antonia Ribes^3,4, Michio Hirano¹

1: Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; 2: Seattle Children’s Hospital, Seattle, WA, USA; 3: Section of Inborn Errors of Metabolism-IBC. Department of Biochemistry and Molecular Genetics. Hospital Clinic de Barcelona-IDIBAPS, Barcelona.; 4: Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona; 5: Muscle Research and Mitochondrial Function Lab, Cellex - IDIBAPS. Faculty of Medicine and Health Science - University of Barcelona (UB), Barcelona.; 6: Department of Internal Medicine, Hospital Clínic of Barcelona.; 7: Vall d’Hebron Research Institute, Autonomous University of Barcelona, Barcelona, Spain.; 8: Department of Genome Sciences, University of Washington, Seattle, WA, U.S.A.

Metabolic adaptations of respiratory chain organization and function

Erika Fernandez-Vizarra^1,2

1: Department of Biomedical Sciences, University of Padova, Italy; 2: Veneto Institute of Molecular Medicine, Padova, Italy

Pluripotent stem cells and brain organoids for drug discovery of mitochondrial diseases

Alessandro Prigione

Heinrich Heine University, Düsseldorf, Germany

High-throughput single cell analysis reveals progressive mitochondrial DNA mosaicism developing throughout life

Angelos Glynos^1,2, Lyuba V. Bozhilova^1,2, Michele Frison^1,2, Stephen P. Burr^1,2, James B. Stewart³, Patrick F. Chinnery^1,2

1: Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 2: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 3: Biosciences Institute, Faculty of Medical Sciences, Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK

A coordinated multiorgan metabolic response contributes to human mitochondrial myopathy.

Guido Primiano³, Nneka Southwell¹, Viraj Nadkarni¹, Emelie Beattie¹, Maria Lucia Valentino⁴, Valerio Carelli⁴, Serenella Servidei³, Giovanni Manfredi¹, Qiuying Chen², Marilena D'Aurelio¹

1: Weill Cornell Medicine, Brain and Mind Research Institute, New York, NY; 2: Weill Cornell Medicine, Department of Pharmacology, New York, NY; 3: Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy; 4: IRCCS, Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy

Succinylation as a novel pathogenic mechanism in a children's mitochondrial brain disease

Pieti Elonkirjo¹, Tuomas Kukkonen¹, Juan Liu², Jason W. Locasale², Sami Jalil¹, Birgit Schilling³, Eric Verdin^3,4, Marco Reidelbach⁵, Outi Haapanen⁵, Vivek Sharma^5,6, Elsebet Oestergaard⁷, Rosalba Carrozzo⁸, Berge Minassian^9,10, Anu Suomalainen¹

1: STEMM, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; 2: Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA; 3: Buck Institute for Research on Aging, Novato, CA 94945, USA; 4: Gladstone Institutes and University of California, San Francisco, CA 94158, USA; 5: Department of Physics, University of Helsinki, Finland; 6: HiLIFE Institute of Biotechnology, University of Helsinki, Finland; 7: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark; 8: Unit of Cellular Biology and Mitochondrial Diseases, “Bambino Gesù” Children's Hospital, IRCCS, Rome, Italy; 9: Program in Genetics and Genome Biology, The Hospital for Sick Children, Institute of Medical Science University of Toronto, Toronto, Ontario, Canada; 10: Division of Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, USA

The levels and activation state of the pyruvate dehydrogenase complex modulate the SCAFI-dependent organization of the mitochondrial respiratory chain

Sandra Lopez-Calcerrada¹, Ana Sierra-Magro¹, Erika Fernández-Vizarra², Cristina Ugalde^1,3

1: Instituto de Investigación Hospital 12 de Octubre, Madrid 28041, Spain; 2: Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy; 3: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid, Spain

Oxphos deficiency indicates novel functions for the mitochondrial protein import subunit tim50

Jordan J Crameri¹, Catherine S Palmer¹, David Coman², David A Stroud¹, David R Thorburn^3,4,5, Ann E Frazier^3,4, Diana Stojanovski¹

1: Department of Biochemistry and Pharmacology and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, 3010, Australia; 2: Queensland Children’s Hospital, Department of Metabolic Medicine, South Brisbane, Brisbane, Queensland, 4001, Australia; 3: Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia; 4: Department of Paediatrics, University of Melbourne, Melbourne, Victoria, 3052, Australia; 5: Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia

Microproteins in metabolic regulation

Jiemin Nah¹, Baptiste Kerouanton¹, David Robinson², Kyle Dunlap³, Pooja Sridnivasan¹, Sonia Chothani¹, Greg Ducker³, Owen Rackham⁴, David Stroud², Lena Ho¹

1: Duke-NUS Medical School, Singapore; 2: University of Melbourne, Australia; 3: University of Utah, USA; 4: University of Southampton, UK

Decoding the regulatory principles of mitochondrial DNA: packaging, expression, and impact on cellular metabolism

L. Stirling Churchman

Harvard Medical School, United States of America

Mechanisms of mitochondrial RNA biogenesis in health and disease

Hauke Hillen^1,2

1: Department of Cellular Biochemistry, University Medical Center Göttingen, Germany; 2: Research Group Structure and Function of Molecular Machines, Max-Planck-Institute for Multidisciplinary Sciences Göttingen, Germany

Disruption of mitochondrial function induces cell lineage-specific compensatory transcriptional responses during early embryonic development

Stephen P. Burr^1,2, Florian Klimm^1,2,3, Angelos Glynos^1,2, Malwina Prater^1,2,4, Maria Falkenberg⁵, Michal Minczuk², James B. Stewart^6,7, Patrick F Chinnery^1,2

1: Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 2: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 3: Novo Nordisk Research Centre Oxford, Innovation Building, University of Oxford, Old Road Campus, Oxford, UK; 4: Functional Genomics Centre, Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK; 5: Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden; 6: Max Planck Institute for Biology of Ageing, Cologne, Germany; 7: Biosciences Institute, Faculty of Medical Sciences, Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK

Single-cell multi-omics reveals dynamics of purifying selection of pathogenic mitochondrial DNA across human immune cells

Caleb A. Lareau^1,2,3,4,5, Sonia M. Dubois⁵, Frank A. Buquicchio¹, Yu-Hsin Hsieh^6,7, Kopal Garg^4,5, Pauline Kautz^6,7,8, Lena Nitsch^6,7,9, Samantha D. Praktiknjo^6,7, Patrick Maschmeyer^6,7, Jeffrey M. Verboon^4,5, Jacob C. Gutierrez¹, Yajie Yin¹, Evgenij Fiskin⁴, Wendy Luo⁴, Eleni Mimitou^10,17, Christoph Muus^4,11, Rhea Malhotra⁴, Sumit Parikh¹², Mark D. Fleming¹³, Lena Oevermann¹⁴, Johannes Schulte¹⁴, Cornelia Eckert¹⁴, Anshul Kundaje^3,15, Peter Smibert^10,18, Ansuman T. Satpathy^1,2, Aviv Regev^4,16,19, Vijay Sankaran^4,5, Suneet Agarwal⁵, Leif S. Ludwig^4,5,6,7

1: Department of Pathology, Stanford University, Stanford, CA 94305, USA; 2: Parker Institute of Cancer Immunotherapy, San Francisco, CA 94129, USA; 3: Department of Genetics, Stanford University, Stanford, CA 94305, USA; 4: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; 5: Division of Hematology / Oncology, Boston Children’s Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; 6: Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; 7: Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology (BIMSB), 10115 Berlin, Germany; 8: Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany; 9: Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Berlin, Germany; 10: Technology Innovation Lab, New York Genome Center, New York, NY 10013, USA; 11: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02134, USA; 12: Center for Pediatric Neurosciences, Mitochondrial Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; 13: Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; 14: Department of Pediatric Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, Germany; 15: Department of Computer Science, Stanford University, Stanford, CA 94305, USA; 16: Department of Biology and Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; 17: Current address: Immunai, New York, NY 10114, USA; 18: Current address: 10x Genomics, San Francisco, CA 94111, USA; 19: Current address: Genentech, San Francisco, CA 94080, USA

Quantifying mitochondrial proteome remodeling during macrophage polarization

Joan Blanco-Fernandez, Manfredo Quadroni, Alexis A. Jourdain

University of Lausanne, Switzerland

Quantification of all 12 canonical ribonucleotides by real-time fluorogenic in vitro transcription

Janne Purhonen^1,2, Jukka Kallijarvi^1,2

1: Folkhalsan Research Center, Finland; 2: Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki

Long-read NGS for detection of mitochondrial DNA large-scale deletions and complex rearrangements

Chiara Frascarelli¹, Nadia Zanetti¹, Alessia Nasca¹, Rossella Izzo¹, Costanza Lamperti¹, Eleonora Lamantea¹, Daniele Ghezzi^1,2, Andrea Legati¹

1: Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan, Italy); 2: University of Milan (Milan, Italy)

Fuels and drivers of smouldering brain disease

Stefano Pluchino, Luca Peruzzotti-Jametti, Alexandra Nicaise

University of Cambridge, United Kingdom

Immunometabolisms at the crossroad between inflammation and aging

Maria Mittelbrunn

CSIC- Consejo Superior de Investigaciones Cientificas, Spain

Dissecting the role of type I interferon signaling in microglial response in a mouse model of mitochondrial disease

Melania González-Torres^1,2, Patrizia Bianchi¹, Patricia Prada-Dacasa¹, Joaquín Fernández-Irigoyen³, Enrique Santamaría³, Mariona Arberola⁴, Elisenda Sanz^1,2, Albert Quintana^1,2

1: Institute of Neurosciences, Autonomous University of Barcelona, Barcelona, Spain; 2: Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain; 3: Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Pamplona, Spain; 4: Centro de Análisis Genómico, CNAG-CRG, Barcelona, Spain

The contribution of cell free-mitochondrial DNA in the pathogenesis of MELAS syndrome

Alessandra Maresca¹, Monica Moresco¹, Valentina Del Dotto², Concetta Valentina Tropeano¹, Mariantonietta Capristo¹, Claudio Fiorini¹, Danara Ormanbekova¹, Alessandro Rapone², Maria Lucia Valentino^1,2, Chiara La Morgia^1,2, Valerio Carelli^1,2

1: IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Italy; 2: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy

A novel role for the mitochondrial topoisomerase TOP1MT in mediating mtDNA release and cGAS-STING activation

Iman Al Khatib¹, Yves Pommier², Phillip West³, William Gibson⁴, Tim Shutt¹

1: University of Calgary, Canada; 2: National Institutes of Health; 3: Texas A&M University; 4: University of British Columbia

Impaired inflammatory response to lipopolysaccharide in fibroblasts from patients with long-chain fatty acid oxidation disorders

Signe Mosegaard^1,2, Krishna Twayana³, Simone Denis¹, Jeffrey Kroon⁴, Bauke Schomakers⁵, Michel van Weeghel⁵, Riekelt Houtkooper¹, Rikke Olsen², Christian Holm³

1: Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 2: Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 3: Department of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark; 4: Department of Experimental Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 5: Core Facility Metabolomics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands

Fumarate induces mtDNA release via mitochondrial-derived vesicles and drives innate immunity

Vincent Paupe¹, Vincent Zecchini², Christian Frezza^2,3, Julien Prudent¹

1: Medical Research Council, MBU,University of Cambridge, UK; 2: Medical Research Council Cancer Unit,University of Cambridge, UK; 3: CECAD Research Centre, University of Cologne, Cologne, Germany

Free cytosolic-mitochondrial DNA triggers a potent type-I Interferon response in Kearns–Sayre patients counteracted by mofetil mycophenolate

Michela Di Nottia¹, Ivan Caiello², Alessandra Torraco¹, Martina Zoccola¹, Fabrizio De Benedetti², Carlo Dionisi-Vici³, Enrico Bertini⁴, Diego Martinelli³, Rosalba Carrozzo¹

1: Unit of Cellular Biology and Diagnosis of Mitochondrial Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; 2: Division of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3: Division of Metabolism, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 4: Research Unit of Muscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

Destructuring of mitochondrial cristae in the initiation of CHCHD10-related neurodegeneration

Véronique Paquis-Flucklinger^1,2

1: IRCAN, UMR 7284/INSERM U1081/UCA, Nice, France; 2: Reference Center for mitochondrial diseases, Universitary hospital, Nice, France

Convergence of mitochondrial and lysosomal dysfunction in Parkinson’s disease

Lena F Burbulla

Ludwig Maximilian University (LMU) Munich, Germany

Development of cortical organoids to model m.3243A>G disease and understand cell specificity

Denisa Hathazi, Yu Nie, Camilla Lions, Juliane Müller, George Gibbons, Patrick Chinnery, Andras Lakatos, Rita Horvath

University of Cambridge, United Kingdom

Brain and brainstem-specific mitochondrial diversity associated with vulnerability to neurodegeneration in mitochondrial diseases

Anna S. Monzel¹, Masashi Fujita², Ayelet M. Rosenberg¹, Eugene V. Mosharov^3,6, Jack Devine¹, David A. Bennett^4,5, Vilas Menon², Philip L. De Jager², Martin Picard^1,6,7

1: Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York NY, USA; 2: Center for Translational & Computational Neuroimmunology, Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical Center, New York NY, USA; 3: Division of Molecular Therapeutics, Department of Psychiatry, Columbia University Irving Medical Center, New York NY, USA; 4: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; 5: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; 6: New York State Psychiatric Institute, New York NY, USA; 7: Department of Neurology, Columbia University Irving Medical Center, New York NY, USA

Mitochondrial DNA mutations exacerbate motor and behavioural deficits in a mouse model of Parkinson’s disease

Michael J Keogh^1,2, Yu Nie^2,3, Zoe Golder^2,3, Malwina Prater^2,3, Nils-Goran Larsson⁴, Andrew Blamire^1,5, Chris Morris¹, Patrick F Chinnery^2,3

1: Clinical and Translational Research Institute, Centre for Life, Newcastle University, UK, NE3 1BZ; 2: Department of Clinical Neuroscience, University of Cambridge, UK, CB2 0QQ; 3: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK, CB2 0QQ; 4: Division of Molecular Metabolism, Biomedicum, floor 9D, Solnavägen 9, Karlolinska Institute, 171 65 Stockholm, Sweden; 5: Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, NE4 5PL

Macromolecular crowding: A novel player in mitochondrial physiology and disease

Elianne P Bulthuis¹, Cindy EJ Dieteren¹, Jesper Bergmans¹, Job Berkhout¹, Jori A Wagenaars¹, Els MA van de Westerlo¹, Emina Podhumljak¹, Mark A Hink², Laura FB Hesp¹, Hannah S Rosa³, Afshan N Malik³, Mariska Kea-te Lindert¹, Peter HGM Willems¹, Han JGE Gardeniers⁴, Wouter K den Otter⁴, Merel JW Adjobo-Hermans¹, Werner JH Koopman^1,5

1: Radboud University Medical Center, The Netherlands; 2: University of Amsterdam, The Netherlands; 3: King's College, London, UK; 4: University of Twente, The Netherlands; 5: Wageningen University, The Netherlands

Preserved motor function and striatal innervation despite severe degeneration of dopamine neurons upon mitochondrial dysfunction

Thomas Paß¹, Roy Chowdury², Julien Prudent², Yu Nie³, Patrick Chinnery³, Markus Aswendt⁴, Heike Endepols⁵, Bernd Neumaier⁵, Trine Riemer⁶, Bent Brachvogel⁶, Rudi Wiesner⁷

1: Center for Physiology and Pathophysiology, Faculty of Medicine and University Hospital Cologne, Germany; 2: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK; 3: Medical Research Council Mitochondrial Biology Unit and Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, UK; 4: Department of Neurology, Faculty of Medicine and University Hospital Cologne, Germany; 5: Institute of Radiochemistry and Experiment Molecular Imaging, Faculty of Medicine and University Hospital of Cologne, Germany; 6: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Faculty of Medicine and University Hospital Cologne, Germany; 7: Center for Physiology and Pathophysiology, Faculty of Medicine and University Hospital Cologne; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD) and Center for Molecular Medicine Cologne, University of Cologne, Germany

The mitochondrial DNA depletion syndrome protein FBXL4 mediates the degradation of the mitophagy receptors BNIP3 and NIX to suppress mitophagy

Keri-Lyn Kozul¹, Giang Thanh Nguyen-Dien^1,2, Yi Cui¹, Prajakta Gosavi Kulkarni¹, Michele Pagano^3,4, Brett M. Collins⁵, Robert Taylor^6,7, Mathew J.K. Jones⁸, Julia K. Pagan^1,5,8

1: School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia; 2: Department of Biotechnology, School of Biotechnology, Viet Nam National University-International University, Ho Chi Minh City, Vietnam; 3: Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, USA; 4: Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, USA; 5: The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia; 6: Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 7: NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 8: The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia

Transcriptional regulation of mitochondrial stress responses

Aleksandra Trifunovic

University of Cologne, Germany

Mitochondrial DNA mutations in ageing and cancer - what's the connection?

Anna Smith¹, Julia Whitehall¹, Shivam Karadkar¹, Pedro Silva-Pinheiro², Conor Lawless¹, Michal Minczuk², Doug Turnbull¹, Owen Sansom³, Laura Greaves¹

1: Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom; 2: MRC Mitochondrial Biology Unit, Cambridge, United Kingdom; 3: CRUK Beatson Institute, Glasgow, United Kingdom

Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria

Janne Purhonen^1,2, Rishi Banerjee^1,2, Vilma Wanne^1,2, Nina Sipari³, Matthias Mörgelin^4,5, Vineta Fellman^1,2,6,7, Jukka Kallijärvi^1,2

1: Folkhälsan Research Center, Finland; 2: Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Finland; 3: Viikki Metabolomics Unit, University of Helsinki, Finland; 4: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Sweden; 5: Colzyx AB, Lund, Sweden; 6: Department of Clinical Sciences, Lund, Pediatrics, Lund University, Sweden; 7: Children’s Hospital, Helsinki University Hospital, Finland

A genetic deficiency screen in vivo reveals rescue mechanisms of mitochondrial dysfunction

Najla El Fissi¹, Florian Rosenberger², Kai Chang¹, Thomas Benedict Barton-Owen³, Zoe Golder³, Matthias Mann², Patrick Chinnery³, Anna Wedell¹, Christoph Freyer¹, Anna Wredenberg¹

1: Karolinska Institutet, Sweden; 2: Max-Planck Institute of Biochemistry, Germany; 3: University of Cambridge, Cambridge Biomedical Campus, UK

Heterochromatin Protein 1 controls gene expression and longevity in response to mitochondrial dysfunction

Patricia de la Cruz Ruiz¹, Hayat Heluani Gahete^1,2, María de los Angeles Ortega De La Torre², María Jesús Rodríguez Palero^1,2, Cristina Ayuso García¹, Shinya Ohta³, Peter Askjaer¹, Marta Artal-Sanz^1,2

1: Andalusian Centre for Developmental Biology (CABD). CSIC-Universidad Pablo de Olavide-Junta de Andalucía. Carretera de Utrera Km 1, 41013 Sevilla, Spain.; 2: Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide. Carretera de Utrera Km 1, 41013 Seville, Spain; 3: Department of Biochemistry, Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.

High fat diet ameliorates the mitochondrial cardiomyopathy of CHCHD10 mutant mice

Hibiki Kawamata, Nneka Southwell, Nicole Sayles, Giovanni Manfredi

Weill Cornell Medicine, United States of America

Functional characterisation of the human mitochondrial disaggregase, CLPB

Megan J Baker¹, Alexander J Anderson¹, Catherine S Palmer¹, David R Thorburn^2,3, Ann E Frazier², Diana Stojanovski¹

1: Department of Biochemistry and Pharmacology, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville VIC 3010, Australia; 2: Murdoch Children’s Research Institute, Royal Children’s Hospital and Department of Paediatrics, The University of Melbourne, Parkville VIC 3052, Australia; 3: Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Parkville VIC 3052, Australia

The mitochondrial inhibitor IF1 has a dual role in cancer

Martina Grandi¹, Cristina Gatto¹, Simone Fabbian², Natascia Tiso³, Francesco Argenton³, Massimo Bellanda², Giancarlo Solaini¹, Valentina Giorgio*¹, Alessandra Baracca*¹

1: Department of Biomedical and Neuromotor Sciences, University of Bologna; 2: Department of Chemical Science, University of Padova; 3: Department of Biology, University of Padova, Padova

Optimising interventional trials: how natural history studies and digital technologies can drive innovation

Gráinne Gorman¹, Michelangelo Mancuso²

1: Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom; 2: University of Pisa, Italy

Identifying circulating biomarkers to monitor mitochondrial disease severity

Rohit Sharma

Massachusetts General Hospital, United States of America

National mitochondrial disease registry in England: linking genetics with routinely collected healthcare data

Katherine R Schon^1,2, Peter Stilwell³, Jeanette Aston³, Robert D S Pitceathly⁴, Michael G Hanna⁴, Carl Fratter⁵, Rita Horvath¹, Mary Bythell³, Steven A Hardy³, Patrick F Chinnery^1,2

1: Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK; 2: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK; 3: National Disease Registration Service, NHS Digital, Leeds, UK; 4: Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; 5: NHS Highly Specialised Services for Rare Mitochondrial Disorders – Oxford Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Status epilepticus in POLG disease

Omar Hikmat^1,2, Karin Naess^3,4, Martin Engvall^3,5, Claus Klingenberg^6,7, Magnhild Rasmussen^8,9,10, Eylert Brodtkorb^11,12, Elsebet Ostergaard¹³, I.F.M de Coo¹⁴, Leticia Pias-Peleteiro¹⁵, Pirjo Isohanni^16,17, Johanna Uusimaa^18,19, Kari Majamaa^20,21, Mikko Kärppä^20,21, Juan Dario Ortigoza-Escobar^22,23, Trine Tangeraas^24,25, Siren Berland²⁶, Rita Horvath²⁷, Niklas Darin²⁸, Shamima Rahman^25,29,30, Laurence A. Bindoff^2,31

1: Department of Paediatrics and Adolescent Medicine, Haukeland University Hospital, Norway; 2: Department of Clinical Medicine (K1), University of Bergen, Norway; 3: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden; 4: Department of Neuropediatrics, Astrid Lindgren Childrens Hospital, Karolinska University Hospital, Stockholm, Sweden; 5: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 6: Department of Paediatric and Adolescent Medicine, University Hospital of North Norway, Tromso, Norway; 7: Paediatric Research Group, Department of Clinical Medicine, UiT- The Arctic University of Norway, Tromso, Norway; 8: Women and Children's Division, Department of Clinical Neurosciences for Children, Oslo University Hospital, Oslo, Norway and Unit for Congenital and Hereditary Neuromuscular Disorders, Department of Neurology, Oslo University Hospital, Oslo, Norway; 9: Department of Neurology, Oslo University Hospital, Oslo, Norway; 10: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 11: Department of Neuroscience and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; 12: Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, Trondheim, Norway; 13: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 14: Facultiy of Health, Medicine and Life Sciences, Department of Toxicology, , University of Maastricht, Maastricht, The Netherlands; 15: Neurometabolic Disorders Unit, Department of Child Neurology/ Department of Genetics and Molecular Medicine, Sant Joan de Déu Children´s Hospital, Barcelona, Spain; 16: Department of Pediatric Neurology, Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 17: Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; 18: Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland; 19: Department of Pediatric Neurology, Clinic for Children and Adolescents and Medical Research Center, Oulu University Hospital, Oulu, Finland; 20: Research Unit of Clinical Medicine, Neurology, and Medical Research Center Oulu, Oulu University hospital and university of Oulu, Oulu Finland; 21: Neurocenter , Oulu University Hospital ,Oulu Finland; 22: Movement Disorders Unit, Institut de Recerca Sant Joan de Déu, CIBERER-ISCIII, Barcelona, Spain; 23: European Reference Network for Rare Neurological Diseases (ERN-RND), Barcelona, Spain; 24: Norwegian national Unit for Newborn Screening, Division of Pediatric and adolescent Medicine, Oslo University Hospital, Oslo, Norway; 25: European Reference Network for Hereditary Metabolic Disorder; 26: Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway; 27: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 28: Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden; 29: Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK; 30: Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 31: Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway

Challenging the norm – outcome measure selection for evaluating therapeutic response in patients with Primary Mitochondrial Myopathy after 12 weeks of treatment with REN001, a novel PPARδ agonist.

Lisa Alcock^1,2, Renae J. Stefanetti^2,3, Oliver Russell^2,3, Alisdair P. Blain^2,3, Jane Newman^2,3,4, Naomi J.P. Thomas^2,3,4, Charlotte Warren^2,3, Huizhong Su^2,3, Philip Brown⁵, David Houghton^2,3, Heather Hunter⁵, Helen Tuppen^2,3, Gavin Falkous⁴, Robert W. Taylor^2,3,4, Albert Z. Lim^2,3,4, Yi Shiau Ng^2,3,4, Catherine Feeney^2,3,4, Iwona Skorupinska⁶, Louise Germain⁷, Enrico Bugiardini⁶, Michael G. Hanna⁶, Robert McFarland^2,3,4, Robert D.S. Pitceathly^6,7, Lynn Rochester^1,2,5, Gráinne S. Gorman^2,3,4

1: Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; 2: National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre (BRC), Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3: Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; 4: NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 5: The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 6: Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; 7: NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK

Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in m.11778G>A MT-ND4 Leber hereditary optic neuropathy patients

Nancy J. Newman¹, Mark L. Moster², Valerio Carelli³, Patrick Yu-Wai-Man⁴, Valerie Biousse¹, Prem S. Subramanian⁵, Catherine Vignal-Clermont⁶, An-Guor Wang⁷, Sean P. Donahue⁸, Bart P. Leroy⁹, Robert C. Sergott², Thomas Klopstock¹⁰, Alfredo A. Sadun¹¹, Gema Rebolleda Fernández¹², Bart K. Chwalisz¹³, Rudrani Banik¹⁴, Magali Taiel¹⁵, José-Alain Sahel¹⁶

1: Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; 2: Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; 3: IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 4: Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 5: Sue Anschutz-Rodgers University of Colorado Eye Center, University of Colorado School of Medicine, Aurora, CO, USA; 6: Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; 7: Department of Ophthalmology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan; 8: Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; 9: Department of Ophthalmology and Center for Medical Genetics, Ghent University Hospital, and Department of Head & Skin, Ghent University, Ghent, Belgium; 10: Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; 11: Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; 12: Department of Ophthalmology, Alcala University, Madrid, Spain; 13: Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA; 14: Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 15: GenSight Biologics, Paris, France; 16: Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France

The mitochondrial stress, brain imaging, and epigenetics study (MiSBIE)

Caroline Trumpff¹, Anna S Monzel¹, Catherine Kelly¹, Kris Engelstad¹, Shufang Li¹, Kalpita Karan¹, Gabriel Sturm¹, Jeremy Michelson¹, Mangesh Kurade¹, Vincenzo Lauriola¹, Sophia Tepler¹, Grace Liu¹, Peter Shapiro¹, Robert-Paul Juster², Stephanie Assuras¹, Richard Sloan¹, Michel Thiebaut de Schotten³, Tor Wager⁴, Michio Hirano¹, Martin Picard¹

1: Columbia University Irving Medical Center, United States of America; 2: Université de Montréal, Canada; 3: Université de Bordeaux, France; 4: Dartmouth College, Uniter States of America

The Organization of the Respiratory Chain and its role in Metabolism

Nils-Göran Larsson

Karolinska Institutet, Sweden

Developing new therapies for mitochondrial diseases

Carlo Viscomi

University of Padova, Italy

AAV-mediated transduction of the nuclear-coded mitochondrial ANT1 gene can ameliorate mouse Ant1-/- pathology: a step toward the treatment of mitochondrial cardiomyopathy

Alessia Angelin^1,2, Kierstin Keller^1,2, Prasanth Potluri^1,2, Deborah Murdock^1,2, Liming Pei^1,2, Douglas C Wallace^1,2

1: The Children's Hospital of Philadelphia, PA USA; 2: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA

Preclinical studies of efficacy and genetic safety of deoxyribonucleosides as a therapy for mitochondrial DNA maintenance defects

Javier Ramón^1,2, Cristina Domínguez-González^2,5, Jordi Leno-Colorado³, Maria Ylla-Català^1,2, Cora Blázquez-Bermejo^1,2, Pau Molla-Zaragoza^1,2, Anne Lombès⁴, Miguel A. Martín^2,5, M.Dolores Sardina⁶, Itxaso Martí⁷, Adolfo López de Munain^8,9, Francina Munell¹⁰, Raúl Juntas¹¹, Juan Luis Restrepo-Vera¹¹, Antònia Ribes^2,12, Anna Karlsson¹³, Antonella Spinazzola¹⁴, Andrés Nascimento^2,15, Marcos Madruga¹⁶, Carmen Paradas^9,17, Elena García-Arumí^1,2,3, Yolanda Cámara^1,2, Ramon Martí^1,2

1: Research Group on Neuromuscular and Mitochondrial Diseases, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Spain; 2: Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; 3: Department of Clinical and Molecular Genetics, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; 4: Institut Cochin, INSERM Unité 1016–Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104–Service de Biochimie Métabolique et Centre de Génétique Moléculaire et Chromosomique, Groupement Hospitalier Universitaire (GHU) Pitié-Salpétrière, Assistance Publique–Hôpitaux de Paris (AP–HP)–Université Paris Descartes, Paris, France; 5: Mitochondrial and Neuromuscular Disorders Group, '12 de Octubre’ Hospital Research Institute (imas12), Madrid, Spain; 6: Pediatric Neurology Department, Badajoz Hospital Complex, Badajoz, Spain; 7: Pediatric Neurology Department, Donostia University Hospital, San Sebastian, Spain; 8: Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián. Neuromuscular Group, Neurosciences Area, Biodonostia Research Institute, San Sebastián, Spain; Neurosciences Department, Basque Country University, San Sebastián, Spain; 9: Centro de Investigación en Red de Enfermedades Neurodegenerativas, CIBERNED (CIBER), Instituto Carlos III, Madrid, Spain; 10: Children Neuromuscular Diseases Unit, Pediatrics, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; 11: Department of Neurology, Neuromuscular Diseases Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; 12: Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, Barcelona, Spain; 13: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; 14: Department of Clinical Movement Neurosciences, Royal Free Campus, University College of London, Queen Square Institute of Neurology, London, UK; 15: Neuromuscular Unit, Neurology Department, Sant Joan de Déu Research Institute, Sant Joan de Déu Hospital, Barcelona, Spain; 16: Neuropediatra, Neurolinkia & Hospital Viamed Santa Ángela De la Cruz, Sevilla, Spain; 17: Neuromuscular Diseases Unit, Neurology Department, Hospital Universitario Virgen del Rocío/ Instituto de Biomedicina de Sevilla, Sevilla, Spain

The mitoDdCBE system as a mitochondrial gene therapy approach

Jose Domingo Barrera-Paez¹, Sandra R. Bacman¹, Till Balla², Beverly Mok³, David Liu³, Danny Nedialkova², Carlos T. Moraes¹

1: University of Miami, United States of America; 2: Max Planck Institute of Biochemistry, Germany; 3: Broad Institute, Harvard University, and HHMI, United States of America

Genetic variants impact on NQO1 expression and activity driving efficacy of idebenone treatment in Leber’s hereditary optic neuropathy cell models

Valentina Del Dotto¹, Serena Jasmine Aleo¹, Martina Romagnoli², Claudio Fiorini², Giada Capirossi¹, Camille Peron³, Alessandra Maresca², Leonardo Caporali², Mariantonietta Capristo², Concetta Valentina Tropeano², Claudia Zanna¹, Anna Maria Porcelli⁴, Giulia Amore², Chiara La Morgia^1,2, Valeria Tiranti³, Valerio Carelli^1,2, Anna Maria Ghelli⁴

1: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 2: IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy.; 3: Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; 4: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.

Peptide mimetic molecules as potential therapeutic agents against diseases related to mt-tRNA point mutations.

Annalinda Pisano¹, Luciana Mosca², Maria Gemma Pignataro¹, Veronica Morea³, Giulia d'Amati¹

1: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Italy; 2: Department of Biochemical Sciences "A. Rossi Fanelli, Sapienza University of Rome, Italy; 3: Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) of Italy

Clinical trials for Leber hereditary optic neuropathy

Nancy J. Newman

Emory University School of Medicine, United States of America

Development of deoxynucleoside therapy for mitochondrial DNA depletion/deletions syndrome

Michio Hirano¹, Caterina Garone², Carlos López-Gomez³, Cristina Domínguez-Gónzalez⁴, Ramon Martí⁵, Agustin Hidalgo-Gutierrez¹

1: Columbia University Irving Medical Center, New York, USA, United States of America; 2: University of Bologna, Bologna, Italy; 3: Univerity of Malaga, Malaga, Spain; 4: University Hospital, 12 de Octubre, Madrid, Spain; 5: Vall d’Hebron Institut de Recerca, Barcelona, Spain

Histopathological and molecular characterization in ocular post-mortem analyses following AAV2 gene therapy for LHON

Valerio Carelli¹, Leonardo Caporali¹, Fred Ross-Cisneros², Elisa Boschetti³, Nancy J. Newman⁴, Valérie Biousse⁴, Henry Liu⁵, Philippe Ancian⁶, Magali Taiel⁷, Alfredo A. Sadun²

1: IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2: Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; 3: IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 4: Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; 5: Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; 6: Charles River Laboratories, Evreux, France; 7: Gensight Biologics, Paris, France

Combatting myopathy in m.3243A>G mutation carriers: first in human transplantation of autologous mesoangioblasts

Florence H.J. van Tienen^1,2, Janneke G.J. Hoeijmakers^2,3, Christiaan van der Leij^4,5, Erika Timmer^1,5, Nikki Wanders^1,2, Fong Lin⁶, Susanne P.M. Kortekaas⁶, Inge M. Westra⁶, Pauline Meij⁶, Appie Wijnen⁷, Wouter M.A. Franssen⁸, Bert O. Eijnde⁸, Catharina G. Faber^2,3, Irenaeus F.M. de Coo^1,2,9, Hubert J.M. Smeets^1,2,5

1: Department of Toxicogenomics, Maastricht University Medical Centre+, Maastricht, The Netherlands; 2: School for Mental Health and Neurosciences (MHeNS), Maastricht University Medical Centre+, Maastricht, The Netherlands; 3: Department of Neurology, Maastricht University Medical Centre+, Maastricht, The Netherlands; 4: Department of Radiology, Maastricht University Medical Centre+, Maastricht, The Netherlands; 5: School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, Maastricht, The Netherlands; 6: Center for Cell and Gene Therapy (CCG), Leiden University Medical Center, Leiden, The Netherlands; 7: Department of Rehabilitation Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands; 8: SMRC – Sports Medicine Research Center, BIOMED - Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium; 9: Neuromuscular and Mitochondrial research center (NeMo), Rotterdam/Maastricht, The Netherlands

PHEMI: Phenylbutyrate Therapy in Mitochondrial Diseases with lactic acidosis: an open label clinical trial in MELAS and PDH deficiency patients.

Silvia Marchet¹, Anna Ardissone², Krisztina Einvag¹, Daniele Sala¹, Eleonora Lamantea¹, Giulia Cecchi³, Vincenzo Montano³, Piervito Lopriore³, Maria Pia Iermito¹, Michelangelo Mancuso³, Costanza Lamperti¹

1: Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Experimental Neuroscience, Unit of Medical Genetics and Neurogenetics, Milan, Italy; 2: Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Pediatric Neurosciences, Milan, Italy; 3: Neurological Institute, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Niacin treatment improves metabolic changes in early-stage mitochondrial myopathy

Kimmo Haimilahti^1,2, Lilli Pihlajamäki¹, Mari Auranen³, Niina Urho³, Päivi Piirilä⁴, Antti Hakkarainen⁵, Min Ni⁶, Kirsi Pietiläinen^7,8, Ralph DeBerardinis⁶, Nahid A. Khan¹, Anu Suomalainen^1,9

1: Research Program for Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2: Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 3: Department of Neurosciences, Helsinki University Hospital, Helsinki, Finland; 4: Department of Clinical Physiology and Nuclear Medicine, Laboratory of Clinical Physiology, Helsinki University Hospital, Helsinki, Finland; 5: HUS Diagnostic Center, Radiology, Helsinki University and Helsinki University Hospital, Helsinki, Finland; 6: Children’s Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; 7: Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 8: Healthy Weight Hub, Abdominal Center, Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 9: Helsinki University Hospital Diagnostic Centre, Helsinki, Finland

Use of lenadogene nolparvovec gene therapy for Leber hereditary optic neuropathy in early access programs

Chiara La Morgia¹, Catherine Vignal-Clermont², Valerio Carelli¹, Michele Carbonelli²³, Rabih Hage³, Mark L. Moster⁴, Robert C. Sergott⁴, Sean P. Donahue⁵, Patrick Yu-Wai-Man⁶, Hélène Dollfus⁷, Thomas Klopstock⁸, Claudia Priglinger⁹, Vasily Smirnov¹⁰, Giulia Amore²³, Martina Romagnoli¹, Catherine Cochard¹¹, Marie-Benedicte Rougier¹², Emilie Tournaire-Marques¹², Pierre Lebranchu¹³, Caroline Froment¹⁴, Frederic Pollet-Villard¹⁵, Marie-Alice Laville¹⁶, Claudia Prospero Ponce¹⁷, Scott D. Walter¹⁸, Francis Munier¹⁹, Pauline Zoppe²⁰, Michel Roux²¹, Magali Taiel²¹, José-Alain Sahel²²

1: IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2: Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; 3: Centre Hospitalier National d’Ophtalmologie des Quinze Vingts, Paris, France; 4: Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; 5: Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; 6: Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 7: Institut de Génétique Médicale d’Alsace, CHU de Strasbourg, Strasbourg, France; 8: Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University, Munich, Germany; 9: University Hospital, Ludwig-Maximilians-University, Munich, Germany; 10: Service Explorations de la Vision et Neuro-Ophtalmologie, CHU de Lille, Lille, France; 11: Service d'Ophtalmologie, CHU de Rennes, Rennes, France; 12: Service d'Ophtalmologie, CHU de Bordeaux, Groupe Hospitalier Pellegrin, Bordeaux, France; 13: Service d'Ophtalmologie, CHU de Nantes, Nantes, France; 14: Service de Neuro-Cognition et Neuro-Ophtalmologie, CHU de Lyon, Lyon, France; 15: Service d'Ophtalmologie, Centre Hospitalier de Valence, Valence, France; 16: Service d'Ophtalmologie, CHU de Caen, Caen, France; 17: Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, USA; 18: Retina Consultants, P.C, Hartford, Connecticut, USA; 19: Service d'Ophtalmologie, Hôpital Ophtalmique Jules-Gonin, Lausanne, Switzerland; 20: Centre Hospitalier de Wallonie Picarde, Tournai, Belgium; 21: GenSight Biologics, Paris, France; 22: Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; 23: Department of Biomedical and Neuromotor Sciences, DIBINEM, Bologna, Italy

Mitochondrial replacement in action

Mary Herbert^1,2, Louise Hyslop², Yuko Takeda¹, Magomet Aushev¹, Meenakshi Choudhary², Jane Stewart²

1: Newcastle University, United Kingdom; 2: Newcastle Fertility Centre

The therapeutic potential of mitochondrial genome engineering

Michal Minczuk

MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK

MitoKO: A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome

Pedro Silva-Pinheiro, Christian D. Mutti, Lindsey Van Haute, Christopher A. Powell, Pavel A. Nash, Keira Turner, Michal Minczuk

MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK

Risk of mtDNA reversal among children born after mitochondrial replacement therapy

Shoukhrat Mitalipov¹, Nuria Marti Gutierrez²

1: Oregon Health & Science University, United States of America; 2: Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, United States of America

Specific elimination of m.3243A>G mutant mitochondria DNA using mitoARCUS

Wendy K. Shoop^1,2, Cassandra L. Gorsuch¹, Emma Sevigny¹, Sandra R. Bacman², Janel Lape¹, Jeff Smith¹, Derek Jantz¹, Carlos T. Moraes²

1: Precision BioSciences - Durham, NC, United States of America; 2: University of Miami - Miami, FL, United States of America

MitoCRISPR/Cas9 shifts mtDNA heteroplasmy not as effective as other site-specific nucleases.

Elvira Zakirova^1,2, Ilya Mazunin³, Elena Kiseleva², Ksenia Morozova^1,2, Konstantin Orishchenko^1,2

1: Novosibirsk State University, Novosibirsk, Russia; 2: Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; 3: Skolkovo Institute of Science and Technology, Moscow, Russia

Prenatal diagnostics for a family with 13513G>A mtDNA mutation associated with Leigh Syndrome

Crystal M Van Dyken¹, Amy Koski¹, Hong Ma¹, Nuria Marti Gutierrez¹, Aleksei Mikhalchenko¹, Rebecca Tippner-Hedges¹, Daniel Frana¹, Paula Amato², Shoukhrat Mitalipov¹

1: Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, United States of America; 2: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health and Science University, United States of America

Improving the diagnosis of mitochondrial disease with public funding for whole genome sequencing

Carolyn M Sue

Neuroscience Research Australia

SLC25A38 is Necessary for Mitochondrial Pyridoxal 5’-Phosphate (PLP) Accumulation

Izabella A. Pena^1,2, Jeffrey S. Shi^1,2, Sarah M. Chang^3,4,5, Samuel Block^3,4, Jason Yang^4,6, Charles H. Adelmann^4,6,7,8, Heather R. Keys⁶, Preston Ge^1,2,5, Isabella Witham^1,2, Grzegorz Sienski⁶, David M. Sabatini⁹, Caroline A. Lewis⁶, Nora Kory¹⁰, Matthew G. Vander Heiden^3,4,11, Myriam Heiman^1,2

1: Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA; 2: Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; 3: David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA; 4: Department of Biology, MIT, Cambridge, MA, USA; 5: Harvard-MIT MD/PhD Program, Boston, MA, USA; 6: Whitehead Institute for Biomedical Research, Cambridge, MA, USA; 7: Cancer Research, Massachusetts General Hospital, Boston MA, USA; 8: Cutaneous Biology Research Center, Massachusetts General Hospital Department of Dermatology, Harvard Medical School, Boston, MA; 9: Unafilliated; 10: Harvard T.H. Chan School of Public Health, Boston, MA, USA; 11: Dana-Farber Cancer Institute, Boston, MA, USA

The transcriptional effects of thyroid hormone T3 on mitochondrial metabolism during neurodevelopment

Chiara Santanatoglia¹, Francesca Ciarpella¹, Giulia Pedrotti¹, Benedetta Lucidi¹, Eros Rossi¹, Elisa De Tomi², Raluca Georgiana Zamfir¹, Giovanni Malerba², Giorgio Malpeli³, Ilaria Decimo¹, Emanuela Bottani¹

1: Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; 3: Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy

Transplanting ipsc-derived mitochondria: a promising approach for treating mitochondrial optic neuropathies

Jasmine Harley, Jeremy Pang, Queenie Tan, Alexander Han, Winanto Ng, Cheryl Lee, Zheng Shan Chong, Cheryl Lee, Su Xinyi, Boon Seng Soh, Shi-Yan Ng

Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore 138673, Singapore

The heme exporter FLVCR1a regulates ER-mitochondria membranes tethering and mitochondrial calcium handling

Francesca Bertino¹, Dibyanti Mukherjee², Massimo Bonora³, Jeannette Nardelli⁴, Nicolas Santander Grez⁵, Andreas Hentschel⁶, Elisa Quarta¹, Pierre Gressens⁴, Chiara Riganti⁷, Paolo P Pinton³, Andreas Roos⁸, Thomas Arnold², Emanuela Tolosano¹, Deborah Chiabrando¹

1: University of Turin, Department of Molecular Biotechnology and Health Sciences; 2: Department of Pediatrics, University of California San Francisco, San Francisco, United States; 3: Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy; 4: Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France; 5: Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile; 6: Leibniz Institute of Analytical Sciences, ISAS, Dortmund, Germany; 7: Department of Oncology, University of Torino, Italy; 8: Department of Pediatric Neurology, Developmental Neurology, and Social Pediatrics, Center for Neuromuscular Disorders in Children and Adolescents, University of Duisburg-Essen, Essen, Germany

Host-microbiome co-adaptation to severe nutritional challenge

Subhajit Singha¹, Maxim Itkin², Sergey Malitsky², Yoav Soen¹

1: Department of Biomolecular Sciences, Weizmann Institute of Science, Israel; 2: Life Sciences Core Facilities, Weizmann Institute of Science, Israel

Identification of autophagy as a functional target suitable for the pharmacological treatment of MPAN in vitro

Enrica Zanuttigh¹, Kevork Derderian¹, Miriam A. Güra¹, Arie Geerlof², Ivano Di Meo³, Chiara Cavestro³, Stefan Hempfling^4,5, Stephanie Ortiz-Collazos^4,5, Mario Mauthe^6,7, Tomasz Kmieć⁸, Eugenia Cammarota⁹, Maria Carla Panzeri⁹, Thomas Klopstock^10,11,12, Michael Sattler^4,5, Juliane Winkelmann^1,13, Ana C. Messias^4,5, Arcangela Iuso^1,13

1: Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 2: Protein Expression and Purification Facility, Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 3: Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy; 4: Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 5: Bavarian NMR Centre, Department of Bioscience, School of Natural Sciences, Technical University of Munich, 85747 Garching, Germany; 6: Molecular Cell Biology Section, Department of Biomedical Sciences of Cells & Systems, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands; 7: Expertise Center Movement Disorders Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands; 8: Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; 9: Alembic, Experimental Imaging Center, IRCCS San Raffaele Hospital, 20132 Milan, Italy; 10: Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-University (LMU), 80336 Munich, Germany; 11: Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany; 12: German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; 13: Institute of Human Genetics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany

Nuclear genetic control of mtDNA homeostasis revealed from >250,000 human genomes

Rahul Gupta

Broad Institute; Mass Gen Hospital, Harvard Medical School

Promises and Perils of mitochondrial DNA Gene Editing

Carlos Moraes¹, Bacman Sandra¹, Wendy Shoop², Jose Domingo Barrera Paez¹, Milena Pinto¹, Jeff Smith², Derek Jantz², Cassandra Gorsuch²

1: University of Miami, United States of America; 2: Precision Biosciences, United States of America

Control of mitochondrial protein import

Thomas Becker

University of Bonn, Germany

Quo vadis, mitochondrial medicine

Anu Suomalainen

Helsinki-Finland