Conference Agenda

Precision Medicine Applied to Leigh Syndrome: development of an In Utero fetal gene therapy approach

Alessia Di Donfrancesco¹, Anastasia Giri², Simona Boito², Ivano Di Meo¹, Alessia Adelizzi¹, Carlo Viscomi³, Massimo Zeviani⁴, Valeria Tiranti¹, Roberto Duchi⁵, Cesare Galli⁵, Nicola Persico², Dario Brunetti^1,6

¹Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Italy; ²Fetal Medicine and Surgery Service, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.; ³Department of Biomedical Sciences, University of Padova, Italy; ⁴Department of Neurosciences, University of Padova, Italy; ⁵Laboratorio di Tecnologie della Riproduzione, Avantea, Cremona, Italy; ⁶Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy

AAV-based liver-targeted gene therapy for MNGIE: proposal for a clinical trial

Jelle van den Ameele^1,2, Emma Cutting², Ramon Marti³

¹MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK; ²Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK; ³Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, and Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Catalonia

Experimental model for studying clinical variability of Thymidine Kinase 2 deficiency with induced pluripotent stem cells

Erika Santi¹, Sara Resciniti¹, Gaia Tioli², Sara Carli¹, Flavia Palombo³, Luisa Iommarini², Caterina Garone^1,4

¹Alma Mater Studiorum University of Bologna, Department of Medical and Surgical Sciences, Bologna, Italy; ²Alma Mater Studiorum University of Bologna, University of Bologna, Department of Pharmacy and Biotechnology, Bologna, Italy; ³IRCCS Istituto delle Scienze Neurologiche, Programma di Neurogenetica, Bologna, Italy; ⁴IRCCS Istituto delle Scienze Neurologiche, UOC Neuropsichiatia dell'età pediatrica, Bologna, Italy

Mitochondrial genome variability in COVID-19 patients

Alessia Fiorentino¹, Claudio Fiorini¹, Danara Ormandekova¹, Alessandro Mattiaccio², Paola Dimartino², Edoardo Spagnolo², Orchestra Genomics Group¹, Maddalena Giannella³, Pierluigi Viale³, Zaira R. Palacios-Baena⁴, Tommaso Pippucci⁵, Marco Seri^2,5, Leonardo Caporali⁶, Valerio Carelli^1,6

¹Azienda USL di Bologna - IRCCS Istituto delle scienze Neurologiche di Bologna, Italy, Italy; ²Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, BO, Italy; ³Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ⁴Unit of Infectious Diseases and Clinical Microbiology, University Hospital Virgen Macarena, Institute of Biomedicine of Seville (IBIS)/CSIC, Seville, Spain; ⁵Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ⁶Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy

Decoding the role of optic atrophy1 (OPA1) non-synonymous single nucleotide polymorphisms in mitochondrial DNA maintenance defects

Cuckoo Teresa Jetto, Vissapragada Madhuri, Ritoprova Sen, Ravi Manjithaya

Jawaharlal Nehru Centre for Advanced Scientific Research, India

Feasibility, safety, and efficacy of Ketogenic Diet in patients with mitochondrial myopathy

Heidi. E.E. Zweers^1,2, Sophie H. Kroesen³, Gijsje Beerlink^1,2, Elke Buit^2,4, Karlijn Gerrits^1,2, Astrid Dorhout^1,2, Annemiek M.J. van Wegberg^1,2, Mirian C.H. Janssen^2,4, Saskia B. Wortmann^2,5, Silvie Timmers⁶, Christiaan Saris^2,7

¹Department of Gastroenterology and Hepatology-Dietetics, Radboudumc, Nijmegen, The Netherlands; ²Radboud Centre for Mitochondrial Medicine (RCMM) , Nijmegen, The Netherlands; ³Department of Physiology, Radboudumc, Nijmegen, The Netherlands; ⁴Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands; ⁵University Children’s Hospital, Paracelsus Medical University, Salzburg, Austria; ⁶Human and Animal Physiology, Wageningen University, The Netherlands; ⁷Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands

Degrading factors of mitoribosome quality control and their mitigation of translation-induced stress

Jonathan Meyrick¹, Uwe Richter^1,2, Ana Andjelkovic¹, Omid Safronov², Rob Taylor¹

¹Wellcome Centre for Mitochondrial Research, United Kingdom; ²University of Helsinki

Mitochondrial DNA Double-Strand Breaks lead to the formation of mtDNA deletions which are increased by MgmeI knockout in vivo.

Tania Arguello-Saenz, Nadee Nissanka, Carlos Moraes

University of Miami, United States of America

Mutating the binding interphases of SLIRP and LRPPRC uncover specific roles for these proteins in optimizing mitochondrial translation.

Diana Rubalcava-Gracia¹, Fredrik Levander², Camilla Koolmeister¹, Nils-Göran Larsson¹

¹Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; ²National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Lund University, Lund 223 87, Sweden

A disease-causing mutation (p.F907I) reveals a novel pathogenic mechanism for POLG-related diseases.

Bertil Macao¹, Direnis Erdinc¹, Sebastian Valenzuela¹, Nicole Lesko², Karin Naess², Helene Bruhn², Anna Wedell², Anna Wredenberg³, Maria Falkenberg¹

¹University of Gothenburg, Sweden; ²Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden; ³Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

Mitoribosome intrinsic GTPase mS29 acts as a non-canonical molecular switch to facilitate mitochondrial translation

Samuel Louis Del'Olio¹, Vivek Singh², Alexey Amunts², Antoni Barrientos¹

¹University of Miami, United States of America; ²Stockholm University, Sweden

Nucleoside supplementation in a zebrafish model of RRM2B mitochondrial DNA depletion syndrome alleviates disease associated symptoms.

Benjamin Munro, Declan Hines, Juliane Müller, Rita Horvath

Department of Clinical Neurosciences, University of Cambridge, United Kingdom

Non-stop mRNAs generate a ground state of mitochondrial gene expression noise

Guleycan Lutfullahoglu Bal, Brendan J. Battersby

Institute of Biotechnolgy, University of Helsinki, Finland

Biochemical characterisation of pathological TOP3A variants associated with adult-onset mitochondrial disease

Alejandro Rodriguez Luis^2,3, Direnis Erdinc¹, 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. Nicholls^2,3

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

How hot can mitochondria be? Incubation at temperatures above 43 ºC induces the degradation of respiratory complexes and supercomplexes in intact cells and isolated mitochondria

Raquel Moreno-Loshuertos^1,2, Joaquín Marco-Brualla^1,3, Patricia Meade^1,2, Ruth Soler-Agesta¹, José Antonio Enriquez^4,5, Patricio Fernández-Silva^1,2

¹Department of Biochemistry and Molecualr and Cellular Biology, Universidad de Zaragoza, Spain; ²Institute for Biocomputation and Physics of Complex Systems (BIFI), Zaragoza, Spain; ³Peaches Biotech Group, Madrid, Spain; ⁴Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; ⁵Centro de Investigaciones Biomédicas en Red en Fragilidad y Envejecimiento Saludable, Madrid, Spain

Inhibition of mitochondrial protein Synthesis induces Biosynthesis of oxidative phosphorylation Complex V

Seungtae Lee, Jana Aref, Jan-Willem Taanman

University College London, United Kingdom

Linear DNA driven recombination in human mitochondria.

Georgios Fragkoulis¹, Anu Hangas¹, Craig Mitchel², Carlos Moraes³, Smaranda Wilcox⁴, Jack Griffiths⁴, Steffi Goffart¹, Jaakko Pohjoismäki¹

¹University of Eastern Finland, Finland; ²King Abdullah University of Science and Technology (KAUST); ³University of Miami Miller School of Medicine; ⁴University of North Carolina at Chapel Hill

Mitochondrial Topoisomerase 1 in ribonucleotide removal and mtDNA stability

Cyrielle Bader, Erika Kasho, Josefin M. E. Forslund, Katarzina Niedzwiecka, Paulina H. Wanrooij

Umeå University, Sweden

The (in)fidelity of human mitochondrial gene expression

Brendan James Battersby

University of Helsinki, Finland

The role of mitochondrial RNA polymerase in mtDNA replication priming

Georgios Fragkoulis, Anu Hangas, Steffi Goffart

University of Eastern Finland, Finland

Mitochondrial content is significantly reduced during the early stages of human pluripotent stem cell differentiation

Ruben Torregrosa-Muñumer, Jeremi Turkia, Jana Pennonen, Erika Rannila, Jonna Saarimäki-Vire, Timo Otonkoski, Henna Tyynismaa

University of Helsinki, Finland

Loss of RNase H1 in early B cell development induces mitochondrial-based dysfunction

Robert Joseph Crouch¹, Kiran Sakhuja¹, Caitlin Darling¹, Lionel Sanz¹, Hyongi Chon¹, Stella R Hartono², James Iben¹, Louis Dye¹, Susana Martinez Cerritelli¹, Frederic Chedin²

¹DIR Eunice Kennedy Shriver National Institute of Child Health and Human Devlopment; ²Department of Molecular and Cellular Biology, University of Califofnia, Davis

New insights into late-maturation steps of the human mitochondrial small ribosomal subunit

Marleen Heinrichs^1,2, Anna Franziska Finke¹, Hauke Hillen^1,2, Ricarda Richter-Dennerlein^1,2

¹Department of Cellular Biochemistry, University Medical Center Goettingen, Goettingen, Germany; ²Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Goettingen, Goettingen, Germany

Early-stages during large mitoribosomal subunit assembly

Venkatapathi Challa¹, Elena Lavdovskaia^1,2, Paula Prado¹, Hauke Hillen^1,2, Ricarda Richter-Dennerlein^1,2

¹University Medical Center Göttingen, Germany; ²Cluster of Excellence (MBExC), University of Göttingen, Germany

Effect of post-transcriptional modifications of tRNAMet on mitochondrial codon recognition

Gantavya Arora, Kärt Denks, Ekaterina Samatova, Marina Rodnina

Max Planck Institute of Multidisciplinary Sciences, Göttingen, Germany

Establishing the OPA1 role in the mtDNA maintenance in cell models of Dominant Optic Atrophy (DOA)

Penelope Magnoni¹, Serena Jasmine Aleo², Valentina Del Dotto², Javier Ramón³, Claudia Zanna², Ramon Martí³, Alessandra Maresca¹, Valerio Carelli^1,2

¹IRCCS, Istituto delle Scienze Neurologiche di Bologna, Italy - Programma di Neurogenetica; ²DIBINEM, Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Italy; ³Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Raras-CIBERER, Autonomous University of Barcelona, Barcelona, Spain

Mutations affecting the relation between mtDNA synthesis and proofreading by POLγ

Sebastian Valenzuela, Emily Hoberg, Giorgia Ortolani, Ulrika Alexandersson, Bertil Macao, Maria Falkenberg

Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE-405 30 Gothenburg, Sweden

Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation

Taru Hilander¹, Geoffray Monteuuis², Ryan Awadhpersad², Krystyna L. Broda¹, Max Pohjanpelto³, Elizabeth Pyman¹, Sachin K. Singh⁴, Tuula A. Nyman⁴, Isabelle Crevel⁵, Robert W. Taylor^6,7, Ann Saada⁸, Diego Balboa^9,10, Brendan J. Battersby¹¹, Christopher B. Jackson², Christopher J. Carroll¹

¹Genetics Section, Molecular and Clinical Sciences, St George’s, University of London, London, United Kingdom; ²Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; ³Research Programs Unit, Molecular Neurology, Biomedicum, University of Helsinki, • Helsinki, Finland; ⁴Department of Immunology, Institute of Clinical Medicine, University of Oslo and Oslo, University Hospital, Oslo, Norway; ⁵Core Facilities, St George’s, University of London, London, United Kingdom.; ⁶Wellcome Centre for Mitochondrial Research, Translational and Clinical Research • Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; ⁷NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; ⁸Department of Genetics, Hadassah Medical Center & Faculty of Medicine, Hebrew University of Jerusalem. 9112001 Jerusalem Israel.; ⁹Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; ¹⁰Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; ¹¹Institute of Biotechnology, University of Helsinki, Helsinki, Finland

The role of mL45 N-terminus in mitochondrial translation under standard and stress conditions

Eva Nyvltova, Katerina Percy, Michele Brischigliaro, Antonio Barrientos

Department of Neurology, University of Miami, Miller School of Medicine, FL, USA

Characterization of human mitochondrial translation elongation and ribosome recycling factors mtEFG1 and mtEFG2

Céline Bail, Kärt Denks, Shreya A. Ayyub, Marina V. Rodnina

Max-Planck Institute for Multidisciplinary Sciences, Germany

Knock-out of OGG1 in HEK293 cells does not alter the formation of single strand breaks in mitochondrial DNA upon H2O2 treatment

Afaf M. Said¹, Gábor Zsurka^1,2, Genevieve Trombly¹, Wolfram S. Kunz^1,2

¹Institute of Experimental Epileptology and Cognition Research, University of Bonn, Germany; ²Department of Epileptology, University Hospital Bonn, Germany

Ligase 3 is indispensable for repair of oxidative lesions of mtDNA but dispensable for circular genome end ligation

Wolfram S. Kunz, Genevieve Trombly, Afaf Milad Said, Alexei P. Kudin, Gábor Zsurka

University Bonn, Department of Epileptology, Germany

Modulation of mtDNA heteroplasmy through endosomal-mitophagy

Aylin Gökmen^1,2, Mari Bonse^1,2, Parisa Kakanj³, Rudolf Wiesner^1,2, David Pla-Martín^1,2

¹Institute of Physiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; ²Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; ³Institute of Genetics, University of Cologne, Germany

The role of mitoSAM in mitochondrial gene expression

Ruth Inge Carlton Glasgow¹, Florian Rosenberger², Vivek Singh¹, Alissa Willhalm³, David Moore¹, Marco Moedas^1,4, Miriam Cipullo¹, Joanna Rorbach¹, Anna Wedell⁴, Ilian Atanassov⁵, Alexey Amunts³, Christoph Freyer¹, Anna Wredenberg^1,4

¹Division of Molecular Metabolism, Karolinska Institutet, Stockholm, Sweden; ²Max Planck Institute of Biochemistry, Munich, Germany; ³Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Sweden; ⁴Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden; ⁵Proteomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany

The slumbering mitochondrion awakes: monitoring mitochondrial gene expression during oocyte and early embryo development

Olga Gumenyuk^1,2, Mary Herbert¹, Robert N. Lightowlers², Zofia M. A. Chrzanowska-Lightowlers²

¹Newcastle Fertility Centre, International Centre for Life, Newcastle upon Tyne, NE1 3BZ, United Kingdom; ²Wellcome Centre for Mitochondrial Research, Newcastle University Biosciences Institute, Newcastle upon Tyne, NE2 4HH, United Kingdom

How mitochondrial DNA metabolism shapes cellular senescence

Valentin L'Hôte, Sjoerd Wanrooij

Department of Medical Biochemistry and Biophysics, Umeå University, Umeå 90736, Sweden

Processing of stalled replication forks in mitochondria

Koit Aasumets, Jaakko Pohjoismäki, Steffi Goffart

University of Eastern Finland, Finland

Stochastic survival of the densest accounts for the expansion of mitochondrial mutations in the ageing of skeletal muscle fibres

Ferdinando Insalata¹, Hanne Hoitzing¹, Juvid Aryaman¹, Nick Jones^1,2

¹Department of Mathematics, Imperial College London, United Kingdom; ²EPSRC Centre for the Mathematics of Precision Healthcare, Imperial College London, United Kingdom

Top3α is the replicative topoisomerase in mitochondrial DNA replication

Anu Hangas¹, Alisa Potter^1,2, Craig Michell¹, Johannes Spelbrink², Jaakko Pohjoismäki¹, Steffi Goffart¹

¹University of Eastern Finland, Finland; ²Radboud Center for Mitochondrial Medicine, Department of Paediatrics, Radboudumc, Nijmegen, The Netherlands

Mitochondrial-nuclear compatibility in hare cybrids

Riikka Pauliina Tapanainen¹, Jaakko Pohjoismäki¹, Kateryna Gaertner², Eric Dufour², Craig Michell¹, Sina Saari²

¹University of Eastern Finland, Finland; ²Tampere University, Finland

Identification of drugs for the treatment of POLG-related diseases by means of a high throughput drug repurposing approach performed in Saccharomyces cerevisiae

Enrico Baruffini¹, Tiziana Lodi¹, Raquel Brañas Casas², Giovanni Risato², Francesco Argenton², Natascia Tiso², Alexandru Ionut Gilea¹

¹Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; ²Department of Biology, University of Padova, Padova, Italy

Mitochondrial genome replacement can rejuvenate aging cells

Toshihiko Taya, Akira Shikuma, Ryotaro Maeda, Daisuke Kami, Satoshi Gojo

Kyoto prefectural University of Medicine, Japan

Project pearl: raising the profile of mitochondrial disease

Lyndsey Butterworth, Renae Stefanetti, Julie Murphy, Amanda Temby, Grainne Gorman

Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom

Innovative technology for regulating mitochondrial function in host cells

Yuma Yamada^1,2, Momo Ito¹, Mitsue Hibino^1,3, Daisuke Sasaki⁴, Hideyoshi Harashima¹

¹Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; ²FOREST Program, Japan Science and Technology Agency Japan, Saitama, Japan; ³Faculty of Engineering, Hokkaido University, Sapporo, Japan; ⁴Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

CNS gene therapy in a mouse model of complex I encephalopathy

Brittni Rae Walker, Milena Pinto, Lise-Michelle Theard, Sandra R Bacman, Carlos T Moraes

University of Miami, United States of America

Strategies for fighting mitochondrial diseases: AAV-based gene therapy

Samantha Corra'^1,2, Raffaele Cerutti^1,2, Valeria Balmaceda^1,3, Carlo Viscomi^1,3, Massimo Zeviani^1,2

¹Venetian Institute of Molecular Medicine, Padova; ²Department of Neuroscience, University of Padova; ³Department of Biomedical Sciences, University of Padova

Cannabidiol ameliorates mitochondrial disease via PPARgamma activation

Emma Puighermanal¹, Marta Luna¹, Andrea Urpi¹, Patrizia Bianchi¹, Isabella Appiah¹, Laura Rodríguez-Pascau², Fabien Menardy¹, Alex Gella¹, Paula Tena-Morraja³, Mariona Alberola⁴, Maria Helena de Donato¹, Gunter van der Walt¹, Marc Martinell², Elisenda Sanz¹, Francesc Soriano³, Pilar Pizcueta², Albert Quintana¹

¹Neuroscience Institute, Autonomous University of Barcelona, Bellaterra, Spain; ²Minoryx Therapeutics SL, Barcelona, Spain; ³Celltec-UB, Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat de Barcelona, Barcelona, Spain; ⁴CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain

Sonlicromanol improves phenotypic changes in models of Selenoprotein N-related myopathies

Herma Renkema¹, Marnix Gorissen³, Julien Beyrath¹, Gert Flik³, Jeroen Schoorl³, Xin Li¹, Bas Pennings¹, Svetlana Pecheritsyna¹, Karlijn Bouman⁴, Nicol Voermans⁴, Ulrike Schara-Schmidt⁵, Jan Smeitink^1,2

¹Khondrion, Nijmegen, The Netherlands; ²Department of Pediatrics, RCMM, RadboudUMC, Nijmegen, The Netherlands; ³Radboud University, Radboud Institute for Biological and Environmental Sciences, Cluster Ecology & Physiology, Department of Animal Physiology, Nijmegen, The Netherlands; ⁴Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; ⁵Department of Pediatric Neurology, Centre of neuromuscular disorders in children and adolescents, University Clinic Essen, University of Duisburg-Essen, Germany

Therapeutic interventions to regulate the Q-junction, 1C metabolism and the neuroinflammatory response.

Pilar González-García¹, Mª Elena Díaz-Casado¹, Agustín Hidalgo-Gutiérrez¹, Laura Jiménez-Sánchez², Eliana Barriocanal-Casado¹, Luis C López¹

¹Physiology Department, Biomedical Research Center, University of Granada, Spain; ²Ibs. Granada, Granada, Spain

Yeast as a model for searching drugs against pathologies caused by mutations in ACO2

Alexandru Ionut Gilea¹, Sonia Figuccia¹, Camilla Ceccatelli Berti¹, Claudio Fiorini², Valerio Carelli^2,3, Leonardo Caporali³, Enrico Baruffini¹

¹Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; ²IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy; ³Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna

MiR-181a/b modulation as a potential therapeutic approach for Stargardt disease treatment

Simona Brillante^1,2, Anna Diana¹, Volpe Mariagrazia¹, Eva Cipollaro¹, Marta Molinari^1,2, Carla Damiano^1,3, Antonietta Tarallo^1,3, Sandro Banfi^1,4, Sabrina Carrella⁵, Alessia Indrieri^1,2

¹Telethon Institute of Genetics and Medicine,Italy; ²Institute for Genetic and Biomedical Research, CNR, Italy; ³Department of Translational Medical Science Federico II University of Naples, Italy; ⁴University of Campania Luigi Vanvitelli, Italy; ⁵Ecosustainable Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, Italy

MitoTALEN reduces mutant mtDNA load in the mouse CNS

Sandra R Bacman¹, Jose Domingo Barrera-Paez¹, Milena Pinto¹, James B Stewart², Carlos T Moraes¹

¹Department of Neurology, University of Miami Miller School of Medicine, Miami USA; ²Wellcome Centre for Mitochondrial Research, Biosciences Institute, Newcastle University, Newcastle UK

Phosphodiesterase 5 inhibitors (PDE5i) as a promising treatment for MT-ATP6 associated mater-nally inherited Leigh Syndrome (MILS)

Marie-Thérèse Henke¹, Annika Zink², Annika Wittich³, Sonja Heiduschka², Giulia Pedrotti⁴, Undine Haferkamp³, Dario Brunetti⁵, Caleb Jerred², Thomas Klopstock⁶, Felix Distelmaier², Chiara La Morgia⁷, Valerio Carelli⁷, Fabian Schumacher⁸, Emanuela Bottani⁴, Ole Pless³, Markus Schuelke¹, Alessandro Prigione²

¹Charité-Universitätsmedizin Berlin, Department of Neuropediatrics, Berlin, Germany; ²Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich Heine Universi-ty, Düsseldorf, Germany; ³Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, ScreeningPort, Hamburg, Germany; ⁴University of Verona, Italy; ⁵Fondazione IRCCS Instituto Neurologico "C. Besta", Milano, Italy; ⁶Ludwig Maximilians University (LMU), München, Germany; ⁷University of Bologna, Italy; ⁸Freie Universität Berlin, Germany

The effect of mitochondrial NMNAT3 overexpression on Alzheimer’s related proteinopathies

Milena Pinto, Carlos Moraes

University of Miami, United States of America

In vitro models to test modulators of cellular NAD+ levels

Shanti Lu-Nath¹, Micol Falabella¹, Yidi Zhang¹, Manal E. Alkahtani², Mine Orlu², Robert D. S. Pitceathly^1,3

¹Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; ²UCL School of Pharmacy, UCL, London, UK; ³NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK

Novel small molecule improves mitochondrial function and mitophagy in a complex III deficiency model.

Cristiane Beninca¹, Lucia Fernández del Rio¹, Matheus Pinto Oliveira¹, Karel Erion², David Rincon Fernandez Pacheco⁵, Jasmine Garza², Mathew Dugan², Sophie Kantor¹, Kathleen Rodgers³, Kevin Gaffney², Amy Wang², Marc Liesa-Roig^1,4, Orian Shirihai¹

¹Department of Medicine, Division of Endocrinology, David Geffen School of Medicine, Los Angeles, USA.; ²Capacity Bio, Los Angeles, USA; ³Department of Pharmacology, Center for Innovations in Brain Science, University of Arizona, USA; ⁴Institut de Biologia Molecular De Barcelona (IBMB-CSIC), Spain.; ⁵Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, USA

Preservation of bioenergetics and inhibition of ferroptosis with the novel compound SBT-588 in Friedreich’s Ataxia cell models

Laura Elizabeth Kropp, Alyssa Handler, Hatim Zariwala, Yunmi Park, Martin Redmon, David A. Brown

Stealth BioTherapeutics, Needham, MA, United States of America

The use of a coenzyme Q10 encapsulated mitochondrial targeting lipid nanoparticle formulation has therapeutic effects on a drug-induced liver injury.

Mitsue Hibino^1,2, Masatoshi Maeki², Manabu Tokeshi², Hideyoshi Harashima¹, Yuma Yamada^1,3

¹Faculty of Pharmaceutical Sciences, Hokkaido University, Japan; ²Faculty of Engineering, Hokkaido University, Japan; ³Fusion Oriented REsearch for disruptive Science and Technology (FOREST) Program, Japan Science and Technology Agency (JST) Japan, Saitama, Japan

In vitro 3D model of mitochondrial myopathy human skeletal muscle

Valeria Di Leo^1,2, Xiomara Fernández-Garibay³, Ainoa Tejedera³, Javier Ramón-Azcón³, Gráinne Gorman^1,4, Oliver Russell^1,2, Amy Vincent^1,2, Juanma Fernández-Costa³

¹Wellcome Centre for Mitochondrial Research, Medical School, Newcastle University, United Kingdom; ²Translational and Clinical Research Institute, Newcastle University, United Kingdom; ³Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, Spain; ⁴NHS Highly Specialised Service for Rare Mitochondrial Disorders, Royal Victoria Infirmary

Metabolic consequences for NAD+ and N- Acetyl cysteine treatment on Mitochondrial myopathy

Nahid Khan¹, Liliya Euro¹, Kimmo Haimilahti¹, Eija Pirinen², Min Ni⁴, Johan Auwerx³, Ralph DeBerardinis⁴, Anu Suomalainen^1,5

¹STEMM, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; ²Diabetes and Obesity Research Unit, Research Programs Unit, University of Helsinki, FIN-00290 Helsinki, Finland; ³Laboratory of Integrative Systems Physiology, École polytechnique fédérale de Lausanne, Lausanne, Switzerland; ⁴Children’s Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; ⁵Helsinki University Hospital Diagnostic Centre, Helsinki 00260, Finland

Silencing the aberrant Coq9 mRNA in the Coq9R239X model normalizes complex Q and restores the mitochondrial phenotype.

Pilar González-García^1,2, Julio Ruiz-Travé¹, Celia Roldán-Lozano¹, Juan M. Martínez-Gálvez^1,3, Eliana Barriocanal-Casado¹, Luis C. López^1,2, Laura Jiménez-Sánchez²

¹Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; ²Ibs.Granada, Spain; ³Biofisika Institute (CSIC,UPV-EHU) and Department of Biochemistry and Molecular Biology, University of Basque Country, Leioa, Spain

A high-content in vitro screening to identify new mitophagy-activating compounds

Giacomo Giacchin¹, Valeria Balmaceda¹, Cristiane Benincá^2,3, Carlo Viscomi¹

¹Department of Biomedical Sciences, University of Padova, Italy; ²Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, USA; ³Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, USA

B-RA targets mitochondria in white adipose tissue and reverses diet-induced obesity

Elena Díaz Casado^1,2, Sergio López Herrador¹, Pilar González García^1,2, Laura Jiménez Sánchez², Sara Torres Rusillo¹, Agustín Hidalgo Gutiérrez¹, Luis Carlos López^1,2

¹Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; ²Ibs. Granada, Granada, Spain

HIF1α is a potentially druggable target for MNGIE disease

Silvia Sabeni, Sara Carli, Francesca Ferraresi, Caterina Garone

Alma Mater Studiorum University of Bologna, Italy

Mitochondrial modulation with Leriglitazone as a potential treatment for Rett syndrome

Uliana Musokhranova, Alfonso Oyarzábal, Cristina Grau, Àngels García Cazorla

Institut de Recerca Sant Joan de Déu, Spain

New nutritional therapies for mitochondrial diseases

Borja Fernández García¹, Marcello Bellusci^1,2,4,7,, Jesús González de la Aleja⁶, Montserrat Morales Conejo^1,2,5,7, Elena Martín Hernández^1,2,4,7, Pilar Quijada Fraile^1,2,4,7, Delia Barrio Carreras^4,7, María Paz Guerrero Molina⁶, Joaquín Arenas^1,2, Miguel A Martín^1,2,3, María Morán^1,2

¹Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital ‘12 de Octubre’ (‘imas12’), Madrid, Spain; ²Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Spain; ³Servicio de Genética, Hospital Universitario ‘12 de Octubre’, Madrid, Spain.; ⁴Unidad Pediátrica de Enfermedades Raras, Hospital Universitario ‘12 de Octubre’, Madrid, Spain.; ⁵Servicio de Medicina Interna, Hospital Universitario ‘12 de Octubre’, Madrid, Spain; ⁶Servicio de Neurología, Hospital Universitario ‘12 de Octubre’, Madrid, Spain; ⁷Centro Nacional de Referencia para Errores Congénitos del Metabolismo (CSUR) y Centro Europeo de Referencia para Enfermedades Metabólica Hereditarias (MetabERN), Madrid, Spain

Pyrroloquinoline quinone exerts neuroprotective effects on retinal ganglion cell degeneration

Alessio Canovai^1,2, James R Tribble¹, Melissa Jöe¹, Rosario Amato², Maurizio Cammalleri², Massimo Dal Monte², Pete A Williams¹

¹Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden; ²Department of Biology, University of Pisa, Pisa, Italy

Quinone compounds in primary mitochondrial disease: acute metabolic effects in human-derived cells in vitro

Shilan Alsaied¹, Shusuke Sekine^1,2, Irene Yee¹, Imen Chamkha^1,3, Sonia Simón Serrano^1,3, Eleonor Åsander Frostner^1,3, Magnus J. Hansson^1,3, Eskil Elmér^1,3

¹Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden; ²Department of Anesthesiology, Tokyo Medical University, Tokyo 160-0023, Japan; ³Abliva AB, Lund, Sweden

A novel therapeutic strategy for mitochondrial Leigh Syndrome

Ritsuko Nakai¹, Henyun Shi¹, Hisashi Ohta², Rick Tsai², Masashi Suganuma², Nicholas Borcherding³, Jonathan R Brestoff³, Takafumi Yokota^1,4

¹Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.; ²Luca Science Inc., Tokyo, Japan.; ³Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.; ⁴Department of Hematology, Osaka International Cancer Institute, Osaka, Japan.

Generation of a new neuronal model of Friedreich’s Ataxia and establishment of a drug screening strategy

Olivier Griso¹, Amélie Weiss¹, Deepika Mokkachamy Chellapandi², Hélène Puccio^1,2

¹Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR7104, Université de Strasbourg, France; ²Institut NeuroMyoGene, UMR5261, INSERM U1315, Université Claude Bernard Lyon I Faculté de médecine, Lyon, France

Downregulation of miR-181a/b ameliorates the Leigh syndrome phenotype in Ndufs4 KO mice

Mariagrazia Volpe^1,2, Simona Brillante^1,3, Roberta Tammaro¹, Mariateresa Pizzo¹, Alessandra Spaziano¹, Sara Barbato¹, Maria De Risi¹, Sabrina Carrella⁴, Elvira De Leonibus^1,5, Sandro Banfi^1,6, Brunella Franco^1,7, Alessia Indrieri^1,3

¹Telethon Institute of Genetics and Medicine, Telethon Foundation, Pozzuoli (NA), Italy; ²European School of Molecular Medicine (SEMM); ³Institute for Genetic and Biomedical Research (IRGB), National Research Council (CNR), Milan, Italy; ⁴Ecosustainable Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, Naples, Italy; ⁵Institute of Biochemistry and Cellular Biology (IBBC), National Research Council (CNR), Monterotondo (RM), Italy; ⁶Dep. of Precision Medicine, University of Campania "L. Vanvitelli", Caserta, Italy; ⁷Dep. of Translational Medicine, University of Naples "Federico II", Naples, Italy

Succinate does not increase reactive oxygen species generation in phosphorylating human mitochondria

Irene Yee¹, Alina Lenzer¹, Shusuke Sekine^1,2, Tianshi Liu¹, Imen Chamkha^1,3, Eskil Elmér^1,3, Johannes Ehinger^1,4

¹Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden; ²Department of Anesthesiology, Tokyo Medical University, Tokyo, Japan; ³Abliva, AB, Lund, Sweden; ⁴Otorhinolaryngology Head and Neck Surgery, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden

Disease modeling and drug screening of mitochondrial complex I disorders: From Podospora anserina to Human

Nolwenn Bounaix¹, Jérémy Richard¹, Olivier Baris¹, Naïg Gueguen¹, Valérie Desquiret-Dumas¹, Arnaud Chevrollier¹, Céline Bris¹, Aurélie Renaud¹, Yann Bausan¹, Laurent Monassier², Guillaume Becker², Estelle Ayme Dietrich², Marc-Alexandre Delia³, Audrey Di Giorgio³, Dominique Bonneau¹, Pascal Reynier¹, Guy Lenaers¹, Stépahne Azoulay³, Véronique Paquis-Flucklinger⁴, Déborah Tribouillard-Tanvier⁵, Nathalie Bonnefoy⁶, Agnès Delahodde⁶, Carole Sellem⁶, Vincent Procaccio¹

¹MITOVASC Institute, CNRS UMR 6015 INSERM U1083, Angers University - Angers (France); ²Pharmacology laboratory UR7296, Strasbourg University - Strasbourg (France); ³Côte d'Azur University, CNRS, Institute of Chemistry- Nice (France); ⁴IRCAN, UMR 7284 INSERM U1081/UCA - Nice (France); ⁵IBGC Institute, CNRS UMR 5095 - Bordeaux (France); ⁶Institute for Integrative Biology of the Cell I2BC, UMR9198, University of Paris-Saclay - Paris (France)

Nifuroxazide rescues deleterious effects of MICOS disassembly in disease models

Sylvie Bannwarth¹, Baptiste Ropert¹, Emmanuelle EC. Genin¹, Sandra Lacas-Gervais², Blandine Madji Hounoum³, Nhu Khanh Dinh⁴, Alessandra Mauri-Crouzet¹, Marc-Alexandre D’Elia⁵, Gaelle Augé¹, Manuel Schiff⁶, Deborah Tribouillard-Tanvier⁷, Laurent Monassier⁸, Vincent Procaccio⁹, Nathalie Bonnefoy⁴, Stéphane Azoulay⁵, Jean-Ehrland Ricci³, Agnès Delahodde⁴, Véronique Paquis-Flucklinger¹

¹IRCAN, UMR 7284/INSERM U1081/UCA, Nice, France; ²Université Côte d’Azur, Centre Commun de Microscopie Appliquée, Nice, France; ³Université Côte d’Azur, Inserm U1065, C3M, Nice, France; ⁴Université Paris Saclay, CEA, CNRS, I2BC, Gif-sur-Yvette, France; ⁵Université Côte d’Azur, CNRS UMR 7272, ICN, Nice, France; ⁶Université Paris Descartes-Sorbonne Paris Cité, Inserm U1163, Imagine Institute, Paris, France; ⁷IBGC, UMR5095 CNRS, Bordeaux, France; ⁸CRBS, UR7296, Strasbourg, France; ⁹Université d'Angers, UMR CNRS 6015 – INSERM U1083, Angers, France

Lithospermum erythrorhizon complexs extract prevents dexamethasone-induced muscle atrophy in mice

Tae Youl Ha, Jiyun Ahn

Korea Food Research Institute, Korea, Republic of (South Korea)

Myocardial regeneration therapy using human cardiosphere-derived cells with activated mitochondria

Masahiro Shiraishi^1,2, Daisuke Sasaki¹, Atsuhito Takeda¹, Mitsue Hibino^2,3, Hideyoshi Harashima², Yuma Yamada^2,4

¹Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; ²Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; ³Faculty of Engineering, Hokkaido University, Sapporo, Japan; ⁴Fusion Oriented REsearch for disruptive Science and Technology (FOREST) Program, Japan Science and Technology Agency (JST) Japan, Saitama, Japan

Quinone compounds in primary mitochondrial disease: in vitro characterization of NQO1-mediated NAD+/NADH modulation

Imen Chamkha^1,3, Lee Webster², Steven J. Moss², Magnus J. Hansson^1,3, Eskil Elmer^1,3

¹Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden; ²Isomerase Therapeutics Ltd, Chesterford Research Park, Cambridge, UK; ³Abliva AB, Lund, Sweden

Metformin in mitochondrial disease patients cardiac cells

Outi Sanna Elina Ryytty, Katriina Kukka-Maaria Nurminen, Riikka Helena Hämäläinen

University of Eastern Finland, Finland

Mavodelpar clinical development program in adult patients with primary mitochondrial myopathy (PMM): results from Phase 1b study and design of ongoing pivotal study (STRIDE).

Robert D.S. Pitceathly^1,2, Renae J. Stefanetti^3,4, Jane Newman^3,4, Alasdair Blain^3,4, Gary Layton⁵, Nicola Regan⁶, Lynn Purkins⁶, Madhu Davies⁶, Alejandro Dorenbaum⁷, Michelangelo Mancuso⁸, Amel Karaa⁹, Gráinne Gorman^3,4

¹Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; ²NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; ³Wellcome Centre for Mitochondrial Research, Newcastle University, UK; ⁴NIHR Newcastle Biomedical Research Centre, Newcastle University, UK; ⁵Paramstat Ltd., UK; ⁶Reneo Pharma Ltd., UK; ⁷Reneo Pharmaceuticals Inc., USA; ⁸Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Italy; ⁹Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Rationale and design of a clinical phase 2a study to evaluate the safety and efficiency of OMT-28 in primary mitochondrial disease

Anne Konkel¹, Janine Lossie¹, Luciana Summo¹, Henk Streefkerk¹, John M Seubert², Wolf-Hagen Schunck³, Robert Fischer¹

¹OMEICOS Therapeutics GmbH, Germany; ²University of Alberta, Canada; ³Max-Delbrueck Center for Molecular Medicine, Germany

Treatment with lenadogene nolparvovec gene therapy results in sustained visual improvement in m.11778G>A MT-ND4-LHON patients: the RESTORE study

Patrick Yu-Wai-Man¹, Nancy J. Newman², Valerie Biousse², Valerio Carelli³, Mark L. Moster⁴, Catherine Vignal-Clermont⁵, Thomas Klopstock⁶, Alfredo A. Sadun⁷, Robert C. Sergott⁴, Magali Taiel⁸, José-Alain Sahel⁹

¹Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; ²Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; ³IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; ⁴Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; ⁵Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; ⁶Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; ⁷Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; ⁸GenSight Biologics, Paris, France; ⁹Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France

Current status of the phase 3 trial of dichloroacetate (DCA) for pyruvate dehydrogenase complex deficiency (PDCD)

Peter W Stacpoole¹, Kathy Dorsey²

¹University of Florida, United States of America; ²Saol Therapeutics, United States of America

Efficacy and safety of elamipretide in subjects with primary mitochondrial disease resulting from pathogenic nuclear DNA mutations (nPMD): phase 3 study design

Amel Karaa¹, Michelangelo Mancuso²

¹Massachusetts General Hospital, Harvard Medical School Boston, MA, United States of America; ²Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Italy

Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing change in visual acuity categories according to mitochondrial DNA mutation and disease phase

Patrick Yu-Wai-Man^1,2,3,4, Valerio Carelli^5,6, Berthold Pemp⁷, Neringa Jurkutė^3,4,8, Livia Tomasso⁹, Xavier Llòria⁹, Thomas Klopstock^10,11,12

¹John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; ²Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; ³Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; ⁴Institute of Ophthalmology, University College London, London, United Kingdom; ⁵IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; ⁶Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; ⁷Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; ⁸The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; ⁹Chiesi Farmaceutici S.p.A., Parma, Italy; ¹⁰German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; ¹¹Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; ¹²Department of Neurology, Friedrich‑Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany

Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing change in visual acuity over time according to mitochondrial DNA mutation and disease phase

Berthold Pemp¹, Patrick Yu-Wai-Man^2,3,4,5, Valerio Carelli^6,7, Neringa Jurkutė^4,5,8, Livia Tomasso⁹, Xavier Llòria⁹, Thomas Klopstock^10,11,12

¹Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; ²John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; ³Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; ⁴Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; ⁵Institute of Ophthalmology, University College London, London, United Kingdom; ⁶IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; ⁷Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; ⁸The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; ⁹Chiesi Farmaceutici S.p.A., Parma, Italy; ¹⁰German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; ¹¹Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; ¹²Department of Neurology, Friedrich‑Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany

Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing the impact of idebenone on rates of recovery and worsening of vision according to primary mitochondrial DNA mutation

Neringa Jurkutė^1,2,3, Patrick Yu-Wai-Man^1,2,4,5, Berthold Pemp⁶, Valerio Carelli^7,8, Xavier Llòria⁹, Livia Tomasso⁹, Thomas Klopstock^10,11,12, Alessio Amadasi⁹

¹Moorfields Eye Hospital NHS Foundation Trust, United Kingdom; ²Institute of Ophthalmology, University College London, London, United Kingdom; ³The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; ⁴John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; ⁵Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; ⁶Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; ⁷IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; ⁸Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; ⁹Chiesi Farmaceutici S.p.A., Parma, Italy; ¹⁰German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; ¹¹Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; ¹²Department of Neurology, Friedrich‑Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany

Enzyme replacement strategy by transplantation in MNGIE: lessons from the updated Bologna case series

Roberto D'Angelo¹, Elisa Boschetti¹, Leonardo Caporali¹, Laura Ludovica Gramegna¹, Giovanna Cenacchi¹, Raffaele Lodi¹, Maria Cristina Morelli², Matteo Cescon², Caterina Tonon¹, Alessia Pugliese³, Maria Teresa Dotti⁴, Francesco Sicurelli⁴, Mauro Scarpelli⁵, Massimiliano Filosto⁶, Carlo Casali⁷, Loris Pironi², Valerio Carelli¹, Roberto De Giorgio⁸, Rita Rinaldi¹

¹IRCCS Istituto Scienze Neurologiche di Bologna, Italy; ²IRCCS Policlinico Sant’Orsola-Malpighi di Bologna, Bologna, Italy; ³Department of Clinical and experimental Medicine, University of Messina, Messina, Italy; ⁴Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena; ⁵Institute of Neurology, University of Verona, Verona, Italy; ⁶Center for Neuromuscular Diseases, Unit of Neurology, ASST "Spedali Civili", Brescia, Italy; ⁷Department of Medico-Surgical Sciences and Biotechnologies, University ‘La Sapienza’, Roma, Italy; ⁸Department of Morphology, Surgery and Experimental Medicine, St. Anna Hospital, University of Ferrara, Ferrara, Italy

Developing mouse models to investigate the molecular mechanisms of POLG-related diseases

Samantha Corra'^1,2, Alessandro Zuppardo^1,3, Louise Jenninger⁴, Raffaele Cerutti^1,2, Pedro Silva-Pinheiro⁵, Valeria Balmaceda^1,3, Sara Volta¹, Massimo Zeviani^1,2, Maria Falkenberg⁴, Carlo Viscomi^1,3

¹Venetian Institute of Molecular Medicine, Padova; ²Department of Neuroscience, University of Padova; ³Department of Biomedical Sciences, University of Padova; ⁴Dept. Medical Chemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg; ⁵Mitochondrial Biology Unit, MRC/University of Cambridge, Cambridge, UK

Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing the impact of idebenone on rates of recovery and worsening of vision according to disease phase

Xavier Llòria¹, Patrick Yu-Wai-Man^2,3,4,5, Valerio Carelli^6,7, Berthold Pemp⁸, Neringa Jurkutė^4,5,9, Livia Tomasso¹, Thomas Klopstock^10,11,12

¹Chiesi Farmaceutici S.p.A., Parma, Italy; ²John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; ³Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; ⁴Moorfields Eye Hospital NHS Foundation Trust, United Kingdom; ⁵Institute of Ophthalmology, University College London, London, United Kingdom; ⁶IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; ⁷Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; ⁸Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; ⁹The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; ¹⁰German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; ¹¹Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; ¹²Department of Neurology, Friedrich Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany

Validation of drug delivery and functional activation to mitochondria in skeletal muscle cell

Itsumi Sato^1,2, Mitsue Hibino^1,3, Daisuke Sasaki^1,2, Atsuhito Takeda², Hideyoshi Harashima³, Yuma Yamada^1,4

¹Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; ²Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; ³Faculty of Engineering, Hokkaido University, Sapporo, Japan; ⁴Fusion Oriented research for disruptive Science and Technology (FOREST) Program, Japan Science and Technology Agency (JST) Japan, Saitama, Japan

Novel approaches to modulate mutant mitochondrial DNA in patient-derived induced-pluripotent stem cells

David F Bodenstein¹, Zoe S Thompson², Jonathan M Palozzi², Thomas R Hurd², Ana C Andreazza^1,3

¹Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; ²Department of Molecular Genetics, University of Toronto, Toronto, Canada; ³Department of Psychiatry, University of Toronto, Toronto, ON, Canada

Evaluation of mtDNA copy number assessment in patients with suspected mitochondrial disease

Kate Sergeant^1,2, Carl Fratter^1,2, Louisa Kent^1,3, Tom Vale³, Anca Alungulese⁴, Conrad Smith^1,2, Philip Hodsdon^1,2, Stefen Brady^1,3, Joanna Poulton^1,5, Victoria Nesbitt¹

¹NHS Highly Specialised Services for Rare Mitochondrial Disorders, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; ²Oxford Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; ³Department of Neurology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; ⁴Department of Neurology, Gregorio Marañón University Hospital, Madrid, Spain; ⁵Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK

Hepatoencephalopathy due to GFM1 mutations: generation of a mouse model and preclinical study of an AAV-based gene therapy for the disease

Miguel Molina-Berenguer^1,2, Ferran Vila-Julià^1,2, Sandra Pérez-Ramos^1,2, Maria Teresa Salcedo-Allende³, Yolanda Cámara^1,2, Diego Herrero-Martínez^4,5, África Vales^4,5, Gloria González-Aseguinolaza^4,5, Javier Torres-Torronteras^1,2, Ramon Martí^1,2

¹Research Group on Neuromuscular and Mitochondrial Diseases, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona - Barcelona (Spain); ²Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III - Madrid (Spain); ³Pathology Department, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona - Barcelona (Spain); ⁴Programa de Terapia Génica y Regulación de la Expresión Génica, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra - Pamplona (Spain); ⁵Instituto de Investigación Sanitaria de Navarra, IdiSNA - Pamplona (Spain)

Neuroglobin overexpression in cerebellar neurons of Harlequin mice improves mitochondrial homeostasis and reduces ataxic behavior

Hélène Cwerman-Thibault¹, Vassilissa Malko-Baverel¹, Gwendoline Le Guilloux¹, Edward Ratcliffe¹, Djmila Mouri¹, Isabel Torres-Cuevas^1,2,3, Ivan Millan^1,2,3, Virginie Mignon⁴, Bruno Saubaméa^4,5, Odile Boespflug-Tanguy¹, Pierre Gressens¹, Marisol Corral-Debrinski¹

¹Université Paris Cité, NeuroDiderot, Inserm, F-75019 Paris, France; ²Neonatal Research Group, Health Research Institute La Fe, 46026 Valencia, Spain; ³Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain; ⁴Université Paris Cité, Platform of Cellular and Molecular Imaging, US25 Inserm, UAR3612 CNRS, 75006 Paris, France; ⁵Université de Paris, UMR-S 1144 Inserm, 75006 Paris, France

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

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

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

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

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

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

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

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

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

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

Host-microbiome co-adaptation to severe nutritional challenge

Subhajit Singha¹, Maxim Itkin², Sergey Malitsky², Yoav Soen¹

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PPAR Gamma Agonist Pioglitazone restores Mitochondrial Quality Control in fibroblasts of PITRM1 deficient patients

Alessia Di Donfrancesco¹, Christian Berlingieri¹, Marta Giacomello², Laurence Bindoff³, Segel Reeval⁴, Paul Renbaum⁴, Filippo Santorelli⁵, Carlo Viscomi⁶, Massimo Zeviani⁷, Daniele Ghezzi¹, Dario Brunetti¹

¹Fondazione IRCCS Istituto Neurologico Carlo Besta, Italy; ²Department of Biology, University of Padua, Italy; ³Department of Clinical Medicine, University of Bergen, Norway; ⁴Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel; ⁵Molecular Medicine, IRCCS Fondazione Stella Maris, Italy; ⁶Department of Biomedical Sciences, University of Padova, Italy; ⁷Department of Neurosciences, University of Padova, Italy

Mitochondrial derived vesicles retain membrane potential and contain a functional ATP synthase

‪Reut Hazan‬‏¹, Dvora Lintzer¹, Tamar Ziv², Koyeli Das¹, Irit Rosenhek-Goldian³, Ziv Porat³, Hila Ben Ami Pilo³, Sharon Karniely⁴, Ann Saada⁵, Neta Regev-Rudzki³, Ophry Pines¹

¹Hebrew university, Israel; ²Technion, Haifa, Israel; ³Weizmann Institute of Science, Rehovot, Israel; ⁴Kimron Veterinary Institute, Bet Dagan, Israel; ⁵Hadassah Medical Center and Faculty of Medicine, Hebrew University, Jerusalem Israel

Metabolic modulation of mitochondrial DNA release in cellular models of Parkin-associated Parkinson’s disease

Gideon Agyeah¹, Paul Antony¹, Kobi Wasner¹, Aleksandar Rakovic², Sandro L Pereira¹, Anne Grünewald^1,2

¹Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; ²Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

ATP synthase c-subunit leak metabolism associated with abnormal mitophagic clearance

Bledi Petriti^1,2, Shobana Subramanian², Pawel Licznerski², K Y Chau¹, Lascaratos Gerassimos¹, Garway-Heath David¹, Jonas Elizabeth²

¹University College London, United Kingdom; ²Yale University , USA

Investigating the role of mitochondrial regulators in sorafenib and lenvatinib resistance in HCC cell line

Silvia Pedretti¹, Francesca Palermo¹, Gabriele Imperato¹, Donatella Caruso¹, Maurizio Crestani¹, Emma De Fabiani¹, Nico Mitro^1,2

¹Department of Pharmacological and Biomolecular Sciences - DiSFeB, University of Milan, Italy; ²Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy

Glucose-derived glutamate drives neuronal differentiation

Laura D'Andrea¹, Matteo Audano¹, Silvia Pedretti¹, Gabriele Imperato¹, Giulia De Cesare¹, Clara Cambria², Flavia Antonucci^2,3, Marine Laporte⁴, Monica Di Luca¹, Elena Marcello¹, Nico Mitro^1,5

¹Department of Pharmacological and Biomolecular Sciences -DiSFeB, Università degli Studi di Milano, Milan, Italy; ²Department of Medical Biotechnology and Translational Medicine - BIOMETRA, Università degli Studi di Milano, Milan, Italy; ³Institute of Neuroscience, IN-CNR, Milan, Italy; ⁴Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland; ⁵Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.