Conference Agenda

Recessive MECR pathogenic variants cause a LHON-like optic neuropathy

Claudio Fiorini¹, Andrea Degiorgi², Maria Lucia Cascavilla³, Concetta Valentina Tropeano¹, Chiara La Morgia^1,4, Marco Battista³, Danara Ormanbekova¹, Flavia Palombo¹, Michele Carbonelli⁴, Francesco Bandello³, Valerio Carelli^1,4, Alessandra Maresca¹, Piero Barboni³, Enrico Baruffini², Leonardo Caporali⁴

¹IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; ²Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; ³Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy; ⁴Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Italy

Variants in ATP5F1B are associated with dominantly inherited dystonia

Alessia Nasca¹, Niccolò Mencacci², Federica Invernizzi¹, Michael Zech³, Andrea Legati¹, Giovanna Zorzi¹, Holger Prokisch³, Steven Lubbe², Barbara Garavaglia¹, Daniele Ghezzi^1,4

¹Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy; ²Northwestern University, Feinberg School of Medicine, Chicago, USA; ³Helmholtz Zentrum München, Technical University of Munich, Munich, Germany; ⁴Università di Milano, Milan, Italy

Toward clinical implementation of quantitative proteomics in the detection of mitochondrial disorders

Daniella H Hock¹, Liana N Semcesen¹, Nikeisha J Caruana^1,2, Sumudu Amarasekera^1,3, Teresa Zhao^1,3,4, Ann E Frazier^1,3, Shabnam Bakhshalizadeh^1,3, Megan Ball^1,3,4, Tegan Stait^3,4, Jessie Jacobsen^5,6, Emma Glamuzina^5,6, Bryony Ryder^5,6, Johan L K Van Hove⁷, Elena Tucker^1,3, Andrew Sinclair^1,3,4, Cas Simons^8,9, Alison G Compton^1,3,4, John Christodoulou^1,3,4, David R Thorburn^1,3,4, David A Stroud^1,3,4

¹University of Melbourne, Parkville, Australia; ²Victoria University, Footscray, Australia; ³Murdoch Children’s Research Institute, Melbourne, Australia; ⁴Victorian Clinical Genetics Services, Melbourne, Australia; ⁵National Metabolic Service Auckland City Hospital, Auckland, New Zealand; ⁶Starship Children's Hospital, Auckland, New Zealand; ⁷University of Colorado, Aurora, United States of America; ⁸Centre for Population Genomics, Melbourne, Australia; ⁹Garvan Institute of Medical Research, Sydney, Australia

A DNM2-related myopathy mimicking a primary mitochondrial disorder

Ignazio Giuseppe Arena¹, Rosalba Carrozzo², Mattia Porcino¹, Alba Migliorato³, Carmelo Rodolico¹, Olimpia Musumeci¹

¹Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.; ²Department of Neurosciences, Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; ³Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Assessing the association of mitochondrial DNA genes with Primary Mitochondrial Disease using the ClinGen Clinical Validity Framework

Elizabeth M. McCormick¹, James T. Peterson¹, Julie P. Taylor², Krista Bluske², Amanda R. Clause², Anjana Chandrasekhar², Josh Lowry², Alison J. Coffey², Xiaowu Gai^3,4, Marni J. Falk^1,5, Zarazuela Zolkipli-Cunningham^1,5, Shamima Rahman⁶

¹Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA; ²Illumina Laboratory Services, Illumina Inc., San Diego, CA; ³Center for Personalized Medicine, Department of Pathology & Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA; ⁴Keck School of Medicine, University of Southern California, Los Angeles, CA; ⁵Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; ⁶Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom

Functional characterisation of the m.8424T>C MT-ATP8 variant using quantitative proteomics

Liana Semcesen¹, Nikeisha Caruana^1,2, Daniella Hock¹, Alison Compton^1,3,4, Zornitza Stark^1,4,5, John Christodoulou^1,3,4, David Thorburn^1,3,4, David Stoud^1,3,4

¹University of Melbourne, Parkville, Australia; ²Victoria University, Footscray, Australia; ³Murdoch Children’s Research Institute, Melbourne, Australia; ⁴Victorian Clinical Genetics Services, Melbourne, Australia; ⁵Australian Genomics, Melbourne, Australia

COX18 variants cause isolated Complex IV deficiency associated with neonatal hypertrophic cardiomyopathy, myopathy and axonal sensory neuropathy

Dario Ronchi¹, Megi Meneri^1,2, Francesca Magri², Francesca Menni², Manuela Garbellini², Maria Francesca Bedeschi², Robertino Dilena², Valeria Cecchetti², Irene Picciolli², Francesca Furlan², Valentina Polimeni², Sabrina Salani², Laura Pezzoli², Francesco Fortunato¹, Matteo Bellini³, Sara Antognozzi², Daniela Piga², Michela Ripolone², Simona Zanotti², Laura Napoli², Patrizia Ciscato², Monica Sciacco², Giovanna Mangili³, Fabio Mosca², Stefania Corti^1,2, Maria Iascone³, Giacomo Pietro Comi^1,2

¹Dino Ferrari Center, University of Milan, Italy; ²IRCCS Cà Granda Ospedale Maggiore Policlinico Milan, Italy; ³ASST Papa Giovanni XXIII, Bergamo, Italy

Severe mitochondrial encephalomyopathy caused by de novo variants in OPA1

Daria Diodato¹, Michela Di Nottia², Alessandra Torraco², Teresa Rizza², Claudia Nesti³, Enrico Baruffini³, Diego Martinelli⁴, Margherita Verardo¹, Adele D'Amico¹, Filippo Maria Santorelli⁵, Enrico Bertini¹, Rosalba Carrozzo²

¹Muscular and Neurodegenerative Disorders Unit, Children Hospital Bambino Gesù; ²Cellular biology and mitochondrial diseases diagnostics, Children Hospital Bambino Gesù; ³Department of Chemistry Life Sciences and Environmental Sustainability, University of Parma; ⁴Metabolism Division, Children Hospital Bambino Gesù, Rome; ⁵Molecular Medicine, IRCCS Stella Maris, Pisa

Bi-allelic TEFM variants are associated with a treatable mitochondrial myopathy

Alessandra Torraco¹, Guido Primiano^2,3, Anastasia Altobelli¹, Teresa Rizza¹, Michela Di Nottia¹, Rosalba Carrozzo¹, Serenella Servidei^2,3

¹Unit of Cellular Biology and Diagnosis of Mitochondrial Disease, Bambino Gesù Children’s Hospital, IRCCS, Rome Italy.; ²Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.; ³Dipartimento Di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.

TOMM40L as a new causative gene for autosomal recessive mitochondrial disease.

Francisco Javier Cotrina Vinagre¹, María Elena Rodríguez García¹, Lucía Del Pozo Filiú¹, Elena Martín Hernández^2,3, Francisco Martínez Azorín^1,3

¹Laboratorio de Enfermedades Mitocondriales. Instituto de Investigación Hospital 12 de Octubre (i+12), E-28041 Madrid, Spain.; ²Unidad Pediátrica de Enfermedades Raras, Enfermedades Mitocondriales y Metabólicas Hereditarias, Hospital 12 de Octubre, E-28041, Madrid, Spain.; ³Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, E-28041 Madrid, Spain.

A primary cardiological phenotype caused by an inherited mtDNA single deletion: a case report from an Italian pedigree

Piervito Lopriore¹, Christiane Neuhofer^2,3, Vincenzo Montano¹, Adriana Meli¹, Annalisa Lo Gerfo⁴, Giulia Cecchi⁴, Maria Adelaide Caligo⁴, Riccardo Berutti^2,3, Robert Kopajtich^2,3, Gabriele Siciliano¹, Holger Prokisch^2,3, Michelangelo Mancuso¹

¹Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy; ²Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; ³Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg, Germany; ⁴Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

Genetic characterization of a large cohort of Spanish patients with TK2 deficiency. A founder effect of two TK2 variants partially contributes to a higher prevalence of the disorder in Spain.

Cristina Domínguez-González^1,2, Pablo Serrano-Lorenzo^1,2, Alberto Blázquez^1,2, Juan Francisco Quesada-Espinosa¹, Jorge Amigo Lechuga³, Pablo Mínguez^2,4, Carmen Ayuso^2,4, Elena García-Arumí⁵, Nuria Muelas^2,6, Teresa Jaijo⁶, Andrés Nascimento⁷, Beatriz Galán-Rodriguez⁸, Carmen Paradas^8,9, Joaquín Arenas^1,2, Ángel Carracedo^2,3, Ramon Martí^2,5, Miguel A. Martin^1,2

¹Hospital Universitario 12 de Octubre, imas12 Research Institute, Madrid, Spain; ²Spanish Network for Biomedical Research in Rare Diseases (CIBERER); ³Fundación Galega de Medicina Xenómica, Santiago de Compostela, Spain; ⁴Instituto de Investigación Sanitaria, Hospital Universitario FundaciónJiménez Díaz, Madrid, Spain; ⁵Research Group on Neuromuscular and Mitochondrial Diseases, Vall d’Hebron Research Institute, Autonomous University of Barcelona, Barcelona; ⁶Hospital Universitari I Politècnic La Fe, Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia; ⁷Sant Joan de Déu Research Institute, Sant Joan de Déu Hospital, Barcelona, Spain.; ⁸Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío, Sevilla, Spain.; ⁹Center for Biomedical Network Research on Neurodegenerative Disorders (CIBERNED)

HSD17B10 interacts with CBR4 to form human mitochondrial 3-ketoacyl-acyl carrier protein reductase 2 (KAR2) in the mitochondrial fatty acid synthesis pathway

Ali Julfiker Md Masud, Guangyu Jiang, Kaija J Autio, J Kalervo Hiltunen, Alexander J Kastaniotis

Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland

Novel atypical variants causing pyruvate dehydrogenase complex deficiency

Helene Bruhn^1,2, Karin Naess^1,2, Sofia Ygberg^2,3, Nicole Lesko^2,4, Rolf Wibom^1,2, Anna Wedell^2,4, Anna Wredenberg^1,2

¹Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; ²Centre of inherited metabolic diseases, Karolinska University Hospital, Stockholm, Sweden; ³Neuropediatric Unit, Dept of Women’s, and Children's Health, Karolinska Institutet, Stockholm, Sweden; ⁴Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Novel genetic discoveries detected using diagnostic OMICSs in patients suspected to suffer from multiple acyl-CoA dehydrogenation deficiency

Signe Mosegaard^1,11, Mirjana Gusic^2,3, Yasuhiko Ago⁴, Xiao Yue⁴, Vincente Yépez^3,5, Julien Gagneur^3,5, Robert Kopajtich³, Dmitrii Smirnov³, Sarah Stenton², Robert Barski⁶, Mark Sharrard⁷, Stanley H. Korman⁸, Jolanta Sykut-Cegielska⁹, Anibh M. Das¹⁰, Helle H. Nygaard¹¹, Margrethe Kjeldsen¹¹, Yusof Rahman¹², Skadi Beblo¹³, Mirian C. H. Janssen¹⁴, Eva Morava¹⁵, Leo A. J. Kluijtmans¹⁶, Alexander Asamoah¹⁷, Emma Buckley¹⁸, Isaque Qureshi¹⁸, Godfrey T. Gillett¹⁹, Ole H. Larsen²⁰, Niels Gregersen¹¹, Toshiyuki Fukao^4,21, Hideo Sasai⁴, Simon Olpin²², Holger Prokisch^2,3, Rikke K. J. Olsen¹¹

¹Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands; ²Institute of Neurogenomics, Helmholtz Zentrum München, Germany; ³Institute of Human Genetics, School of Medicine, Technical University Munich, München, Germany.; ⁴Department of Pediatrics, Graduate School of Medicine, Gifu University Hospital, Gifu, Japan.; ⁵Department of Informatics, Technical University of Munich, Garching, Germany.; ⁶Department of Biochemical Genetics, St James's University Hospital, Leeds, UK.; ⁷Department of Pediatrics, Sheffield Children's Hospital, Sheffield, UK.; ⁸Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel.; ⁹Department of Inborn Errors of Metabolism and Paediatrics, The Institute of Mother and Child, Warsaw, Poland.; ¹⁰Department of Pediatrics, Hannover Medical School, Hannover, Germany.; ¹¹Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.; ¹²Center for Inherited Metabolic Disorders, Guy’s & St Thomas’ Hospital NHS Foundation Trust, London, UK.; ¹³University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.; ¹⁴Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; ¹⁵Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA; ¹⁶Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; ¹⁷UofL Physicians Novak Center for Children's Health, Louisville, USA.; ¹⁸Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham, UK; ¹⁹Sheffield Teaching Hospitals NHS Trust, University of Sheffield, Sheffield, UK; ²⁰Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.; ²¹Clinical Genetics Center, Gifu University Hospital, Gifu, Japan.; ²²Department of Clinical Chemistry, Sheffield Children’s Hospital, Sheffield, UK.

The Australian genomics mitochondrial flagship: a national program delivering mitochondrial diagnoses

David Thorburn^1,2,3, Naomi Baker^2,3, Shanti Balasubramaniam⁴, Stephanie Best⁵, Kaustuv Bhattacharya⁴, Kristen Boggs⁴, Sarah Borrie⁶, Drago Bratkovic⁶, Jeffrey Braithwaite⁵, Alessandra Bray⁴, Jo Burke⁷, David Coman^8,9, Alison Compton^1,2, Mark Cowley¹⁰, Martin Delatycki^2,3, Michelle de Silva^1,2,3, Carolyn Ellaway⁴, Michael Fahey¹¹, Janice Fletcher¹², Leah Frajman^1,2, Ann Frazier^1,2, Velimer Gayeskiv⁹, Roula Ghaoui¹², Himanshu Goel¹³, Ilias Goranitis², Daniella Hock², Denise Howting¹⁴, Matilda Jackson⁶, Maina Kava¹⁵, Sarah King-SMith⁶, Nicole Lake^1,16, Phillipa Lamont^15,17, Joy Lee^2,18, Janet Long⁵, Mandi MacShane¹⁵, Ellenore Martin⁴, Jim McGill⁸, Sean Murray¹⁹, Julie Panetta¹¹, Liza Phillips²⁰, Michael Quinn²¹, Rocio Rius^1,2, Michael Ryan²², Nicholas Smith⁶, David Stroud^1,2,3, Michel Tchan²³, Melanie Tom²¹, Matthew Wallis⁷, Tyson Ware²⁴, AnneMarie Welch¹, Christine Wools¹¹, Eunice Wu², John Christodoulou^1,2,3

¹Murdoch Children's Research Institute, Melbourne, Australia; ²University of Melbourne, Melbourne, Australia; ³Victorian Clinical Genetics Services, Melbourne,; ⁴Sydney Children’s Hospitals Network, Westmead, Australia; ⁵Macquarie University, Sydney, Australia; ⁶Women’s and Children’s Hospital, Adelaide, Australia; ⁷Tasmanian Clinical Genetics Service, Hobart, Australia; ⁸Queensland Children’s Hospital, Brisbane, Australia; ⁹Wesley Hospital, Brisbane, Australia; ¹⁰Garvan Institute, Sydney, Australia; ¹¹Royal Melbourne Hospital, Melbourne, Australia; ¹²Royal Adelaide Hospital, Adelaide, Australia; ¹³John Hunter Hospital, Newcastle, Australia; ¹⁴Harry Perkins Institute of Medical Research, Perth, Australia; ¹⁵Perth Children’s Hospital, Perth, Australia; ¹⁶Yale School of Medicine, New Haven, CT, USA; ¹⁷Royal Perth Hospital, Perth, Australia; ¹⁸Royal Children’s Hospital, Melbourne, Australia; ¹⁹Mito Foundation, Sydney, Australia; ²⁰Mater Hospital, Brisbane, Australia; ²¹Genetic Health Queensland, Brisbane, Australia; ²²Monash University, Melbourne, Australia; ²³Westmead Hospital, Westmead, Australia; ²⁴Royal Hobart Hospital, Hobart, Australia

A new family with a case of severe early-onset muscle fatigue and a peculiar maternally inherited painful swelling in chewing muscles associated with homoplasmic m.15992A>T mutation in mitochondrial tRNAPro

Irene Bruno¹, Elena Ghirigato², Mirko Baglivo³, Francesca Terenzi², Nadia Zanetti³, Massimo Zeviani¹, Eleonora Lamantea³

¹Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy; ²Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy; ³Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

A novel MT-ATP6 variant associated with complicated ataxia in two unrelated Italian patients: case report and functional studies. 

Daniele Sala¹, Silvia Marchet¹, Lorenzo Nanetti¹, Andrea Legati¹, Caterina Mariotti¹, Eleonora Lamantea¹, Daniele Ghezzi^1,2, Alessia Catania¹, Costanza Lamperti¹

¹Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta; ²Department of Pathophysiology and Transplantation (DEPT), University of Milan

Biallelic pathogenic variants of PARS2 cause Developmental and Epileptic Encephalopathy with Spike-and-Wave Activation in Sleep

Laura Licchetta¹, Carlotta Stipa¹, Raffaella Minardi¹, Margherita Santucci^1,2, Lucia Di Giorgi^2,3, Martina Soldà¹, Valerio Carelli^1,2, Francesca Bisulli^1,2

¹IRCCS, Istituto delle Scienze Neurologiche di Bologna, Italy; ²Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy; ³Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Italy.

Novel KARS1 mutation causes early-onset lethal cardiomyopathy

Sara Casalini¹, Silvia Buratti¹, Chiara Panicucci¹, Maria Elena Derchi¹, Marco Scaglione¹, Claudia Nesti², Monica Traverso¹, Francesca Madia¹, Michela Di Nottia³, Chiara Fiorillo¹, Valeria Capra¹, Filippo Maria Santorelli², Andrea Moscatelli¹, Rosalba Carrozzo³, Claudio Bruno¹

¹IRCCS Istituto Giannina Gaslini, Genoa; ²IRCCS Fondazione Stella Maris, Calambrone (PI); ³IRCCS Ospedale Bambin Gesù, Rome

The ER-MITO (Emilia Romagna-Mitochondrial) project: prevalence and genetics of Chronic Progressive External Ophthalmoplegia (CPEO) in an Italian region

Maria Lucia Valentino^1,2, Leonardo Caporali¹, Chiara La Morgia^1,2, Flavia Palombo¹, Martina Romagnoli¹, Cristina Fonti¹, Alessandra Maresca¹, Rocco Liguori^1,2, Corrado Zenesini¹, Roberto D'Alessandro¹, Valerio Carelli^1,2

¹IRCCS Institute of Neurological Sciences of Bologna, Italy; ²Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy

UCHL1 missense and loss-of-function variants as an emerging cause of autosomal dominant optic atrophy (ADOA)

Claudio Fiorini¹, Giada Capirossi^1,2, Eleonora Pizzi¹, Federico Sadun³, Maria Lucia Cascavilla⁴, Chiara La Morgia^1,2, Marco Battista⁴, Piero Barboni⁴, Danara Ormanbekova¹, Valentina Del Dotto², Flavia Palombo¹, Valerio Carelli^1,2, Alessandra Maresca¹, Leonardo Caporali²

¹IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; ²Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Italy; ³Ospedale Oftalmico Roma, Rome, Italy; ⁴Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy

Mitochondrial dysfunction in patients with early-onset UFM1-linked encephalopathy

Samira Ait El Mkadem - Saadi^1,2, Cécile Rouzier^1,2, Annabelle Chaussenot^1,2, Konstantina Fragaki^1,2, Sylvie Bannwarth^1,2, Julien Neveu³, Aline Cano³, Brigitte Chabrol³, Véronique Paquis-Flucklinger^1,2

¹National Centre for Mitochondrial Diseases, Nice Teaching Hospital (CHU de Nice), Department of Medical Genetics, Nice, France; ²Université Côte d'Azur, CHU, Inserm, CNRS, IRCAN, France; ³APHM, La Timone Hospital, Department of Neuropediatrics, Marseille, France

A novel dominant variant in the ISCU gene is associated with mitochondrial myopathy

Joanna Rusecka^1,2, Dominika Szczęśniak^2,3, Magdalena Kacprzak², Damian Loska², Kamila Czerska², Agnieszka Sobczyńska-Tomaszewska²

¹Maria Sklodowska-Curie, Medical Academy in Warsaw, Poland; ²MedGen Medical Center, Warsaw, Poland; ³Institute of Psychiatry and Neurology, Warsaw, Poland

Expanding the spectrum of clinical presentations associated with COA8 pathogenic

Sara Antognozzi¹, Magi Meneri^1,2, Francesca Magri¹, Manuela Garbellini¹, Sabrina Salani¹, Francesco Fortunato², Michela Ripolone¹, Simona Zanotti¹, Patrizia Ciscato¹, Monica Sciacco¹, Stefania Corti^1,2, Giacomo Pietro Comi^1,2, Dario Ronchi²

¹IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; ²Dino Ferrari Center, University of Milan, Milan, Italy

A novel mitochondrial DNA variant, m.14430A>C, in MT-ND6 as the likely cause of Leigh syndrome with mitochondrial complex I deficiency.

Surita Meldau^1,2, Gillian T M Riordan^1,3, Sally Ackermann⁴, Sharika Raga^1,3,6, Careni Spencer^1,5, George F Van der Watt^1,2, Kashief Khan², Francois H Van der Westhuizen⁷

¹University of Cape Town, Cape Town, South Africa; ²National Health Laboratory Sevices, South Africa; ³Red Cross War Memorial Children's Hospital, Cape Town, South Africa; ⁴Constantiaberg Mediclinic, Cape Town, South Africa; ⁵Grootte Schuur Hospital, Cape Town, South Africa; ⁶Neuroscience Institute, University of Cape Town, Cape Town, South Africa; ⁷Human Metabolomics, North-West University, Potchefstroom, South Africa

Leigh syndrome and Fanconi renotubular syndrome are the main clinical phenotype due to mutations in NDUFAF6 gene.

Teresa Rizza¹, Alessandra Torraco¹, Michela Di Nottia¹, Daniela Verrigni¹, Anastasia Altobelli¹, Diego Martinelli¹, Daria Diodato¹, Stephanie Efthymiou², Carlo Dionisi-Vici¹, Enrico Bertini¹, Reza Maroofian², Agnes Rotig³, Rosalba Carrozzo¹

¹Bambino Gesù Children Hospital, Italy; ²UCL Queen Square Institute of Neurology; ³Université Paris Descartes, Sorbonne Paris Cité

Mitochondrial encephalomyopathy associated with the m.618T>C in MT-TF

Aryane Silva Coutinho², Tainara Zappia Tessaro¹, Rodrigo Fonseca Vilanova¹, Celia Harumi Tengan²

¹Hospital Municipal Dr. José de Carvalho, Brazil; ²Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil

TWNK in Parkinson's disease: a Movement Disorder and Mitochondrial Disease Center perspective study

Marco Percetti^1,2,3, Giulia Franco^3,4, Edoardo Monfrini^3,4, Leonardo Caporali⁵, Raffaella Minardi⁵, Chiara La Morgia⁵, Maria Lucia Valentino^5,6, Rocco Liguori^5,6, Ilaria Palmieri⁷, Donatella Ottaviani⁸, Maria Vizziello³, Dario Ronchi³, Federica Di Berardino⁹, Antoniangela Cocco^10,11, Bertil Macao¹², Maria Falkenberg¹², Giacomo Pietro Comi^3,4, Alberto Albanese¹¹, Bruno Giometto⁸, Enza Maria Valente^7,13, Valerio Carelli^5,6, Alessio Di Fonzo^3,4

¹School of Medicine and Surgery and Milan Center for Neuroscience, University of Milan-Bicocca.; ²Foundation IRCCS San Gerardo dei Tintori, Monza; ³Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; ⁴Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy; ⁵IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; ⁶Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; ⁷Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy; ⁸Neurology Unit, Rovereto Hospital, Azienda Provinciale per i Servizi Sanitari (APSS) di Trento, Trento, Italy; ⁹Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Audiology Unit, Milan, Italy; ¹⁰University of Milan, Milan, Italy; ¹¹Department of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas, Research Hospital, Milan, Italy; ¹²Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE 405 30 Gothenburg, Sweden; ¹³Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Novel pathogenic MT-ND3 variant causing a particular MELAS phenotype

Lucile Riera-Navarro¹, Cécile Rouzier¹, Samira Saadi Ait-El-Mkadem¹, Konstantina Fragaki^1,2, Sylvie Bannwarth^1,2, Pierre Thomas³, Luisa Villa⁴, Véronique Paquis Flucklinger^1,2, Annabelle Chaussenot¹

¹CHU de Nice, France; ²Université Côte d'Azur, CNRS, INSERM, IRCAN; ³Service de Neurologie- Hôpital Pasteur 2, CHU de Nice; ⁴Centre de référence des Maladies neuromusculaires

Mitochondrial molecular genetic findings in the South African diagnostic setting

Surita Meldau^1,2, Elizabeth Patricia Owen^1,2, Kashief Khan², Gillian Tracy Riordan³

¹University of Cape Town, Cape Town, South Africa; ²National Health Laboratory Sevices, South Africa; ³Red Cross War Memorial Children's Hospital, Cape Town, South Africa

Known genes, new genes and new phenotypes in inherited mitochondrial eye diseases

Neringa Jurkute^1,2,3, Gavin Arno^1,2,4, Patrick Yu-Wai-Man^1,2,5,6, Andrew R Webster^1,2

¹Moorfields Eye Hospital NHS Foundation Trust, London, UK; ²Institute of Ophthalmology, University College London, London, UK; ³The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK; ⁴North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; ⁵John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; ⁶Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK

LHON spectrum disorder: new phenotypes and genotypes

Marco Battista¹, Leonardo Caporali², Enrico Borrelli¹, Giorgio Lari¹, Alice Galzignato³, Claudio Fiorini², Paolo Nucci⁴, Francesco Bandello¹, Maria Lucia Cascavilla¹, Valerio Carelli^2,5, Piero Barboni¹

¹San Raffaele Hospital, Italy; ²IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica (Bologna, Italy); ³Studio Oculistico d’Azeglio (Bologna, Italy); ⁴Department of Clinical Science and Community Health, University of Milan, (Milan, Italy); ⁵Unit of Neurology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna (Bologna, Italy)

Chronic asymmetric progressive external ophthalmoplegia without eyelid weakness

Jae Ho Jung

Seoul National University Hospital, Korea, Republic of (South Korea)

Bayesian inference enables discovery of functional effects of heteroplasmic mitochondrial mutations in the developing brain

Aidan Scott Marshall, Yue Nie, Nick.S Jones, Patrick.F Chinnery

Imperial College London, United Kingdom

Cell lineage-specific mitochondrial gene expression is established in the early embryo, prior to organ maturation

Stephen P. Burr^1,2, Florian Klimm^1,2,3, Angelos Glynos^1,2, Malwina Prater^1,2,4, James B. Stewart^5,6, Patrick F. Chinnery^1,2, Michele Frison^1,2

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

Identifying mitochondrial methyltransferases using unbiased proteome-ligand profiling

Alissa Wilhalm¹, David Moore¹, Florian Rosenberger¹, Anna Wedell², Christoph Freyer¹, Anna Wredenberg^1,2

¹Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden, Sweden; ²Centre of Inherited metabolic diseases, Karolinska University Hospital, Stockholm, Sweden

Engineering mitochondrial aminoacyl-tRNA synthetases as a tool to investigate mitochondrial protein synthesis

Christin A Albus, Ellyn N Willsher, Syeda Z Akthar, Robert N Lightowlers, Zofia MA Chrzanowska-Lightowlers

Newcastle University, United Kingdom

Short-read NGS for the screening of structural and copy number alterations in mtDNA as powerful diagnostic tool.

Christiane Neuhofer^1,2, Rossella Izzo³, Riccardo Berutti^1,2, Martin Pavlov², Eleonora Lamantea³, Elisabeth Graf¹, Costanza Lamperti³, Thomas Klopstock⁴, Holger Prokisch^1,2, Daniele Ghezzi^3,5, Andrea Legati³

¹Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, (Munich, Germany); ²Institute of Neurogenomics, Helmholtz Zentrum München (Neuherberg, Germany); ³Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan, Italy); ⁴Department of Neurology, Friedrich-Baur-Institute, LMU Hospital, Ludwig Maximilians University (Munich, Germany); ⁵Department of Pathophysiology and Transplantation, University of Milan (Milan, Italy)

Ethical dilemmas and diagnostic uplifts; primary mitochondrial disease the era of first line whole genome sequencing

William L. Macken^1,2, Rachel L. Horton^3,4, Michael G. Hanna^1,2, Anneke M. Lucassen^3,4, Robert D.S. Pitceathly^1,2

¹UCL Queen Square Institute of Neurology, United Kingdom; ²NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK.; ³Centre for Personalised Medicine, and Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; ⁴Clinical Ethics, Law and Society, Faculty of Medicine, University of Southampton, Southampton, UK

Analysis of mitochondrial metabolism using 13C-labeled mass isotopologue analysis and mass spectrometry as a new approach for the diagnostics of mitochondrial disorders

Liesbeth T. Wintjes¹, Arno van Rooij¹, Sacha Hendriks¹, Coby M. Laarakkers¹, Richard J.T. Rodenburg^1,2

¹Department of Genetics, Translational Metabolic Laboratory, Radboudumc, Nijmegen, The Netherlands.; ²Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboudumc, Nijmegen, The Netherlands

Subcellular metabolomics: a pipeline for compartment-specific metabolic investigations in a mouse model of Leigh syndrome

Gunter van der Walt, Jason Elferink, Zander Lindeque, Shayne Mason, Roan Louw

North-West University, South Africa

High‐content screening for modulators of mitochondria‐ER contact sites and identification of their protein targets

Tomas Knedlik¹, Federica Dal Bello¹, Marta Giacomello^1,2

¹Department of Biology, University of Padova, Italy; ²Department of Biomedical Sciences, University of Padova, Italy

A novel Approach to assess the pathogenicity of mtDNA Variants

Omar Tutakhel, Frans van den Brandt, Kai Francke, Hatice Nur Ozhan, Frans Maas, Daan Panneman, Liesbeth Wintjes, Roel Smeets, Dirk Lefeber, Bert van den Heuvel, Richard J. Rodenburg

RadboudUMC, Translational Metabolic Laboratory, Dept of Pediatrics, Nijmegen, The Netherlands

At the core of the apoptotic foci

Hector Flores-Romero, Aida Peña Blanco, Lisa Hohorst, Jonas Aufdermauer, Shashank Dadsena, Cristiana Zollo, Rodrigo Cuevas-Arenas, Ana J. Garcia-Saez.

CECAD, Germany

Clinical utility of ultra-rapid genomic testing for infants and children with a suspected mitochondrial disorder

John Christodoulou^1,2,3,4, Sophie Bouffler⁵, Chirag Patel⁶, Sarah Sandaradura^4,7, Meredith Wilson^4,7,8, Jason Pinner^8,9, Matthew Hunter^10,11, Christopher Barnett^12,13,14, Mathew Wallis^15,16, Benjamin Kamien¹⁷, Tiong Tan^1,2,3, Mary-Louise Freckmann¹⁸, Karin Kassahn^13,14, Tony Roscioli^19,20,21, Alison Compton^1,2,3, David Thorburn^1,2,3, Sebastian Lunke^1,2,3,5, Zornitza Stark^1,2,3,5

¹Murdoch Children's Research Institute, Melbourne, Australia; ²University of Melbourne, Melbourne, Australia; ³Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia; ⁴University of Sydney, Sydney, Australia; ⁵Australian Genomics, Melbourne, Australia; ⁶Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia; ⁷Sydney Children’s Hospitals Network – Westmead, Sydney, Australia; ⁸Sydney Children’s Hospitals Network – Randwick, Sydney, Australia; ⁹University of New South Wales, Sydney, Australia; ¹⁰Monash Genetics, Monash Health, Melbourne, Australia; ¹¹Department of Paediatrics, Monash University, Melbourne, Australia; ¹²Paediatric and Reproductive Genetics Unit, Women’s and Children’s Hospital, North Adelaide, Australia; ¹³Adelaide Medical School, The University of Adelaide, Adelaide, Australia; ¹⁴Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia; ¹⁵Tasmanian Clinical Genetics Service, Tasmanian Health Service, Hobart, Australia; ¹⁶School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; ¹⁷Genetic Services of Western Australia, Perth, Australia; ¹⁸Department of Clinical Genetics, The Canberra Hospital, Canberra, Australia; ¹⁹Centre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia; ²⁰Randwick Genomics Laboratory, NSW Health Pathology, Prince of Wales Hospital, Sydney, Australia; ²¹Neuroscience Research Australia (NeuRA) and Prince of Wales Clinical School, UNSW, Sydney, Australia

Contribution of RNA-seq to diagnosis and determination of functional impact of candidate variants in 45 patients suspected of mitochondrial disease.

Gerard Muñoz-Pujol¹, Olatz Ugarteburu¹, Blai Morales¹, Judit García-Villoria¹, Laura Gort¹, Vicente A. Yépez², Julien Gagneur², Mirjana Gusic², Holger Prokisch², Marc Dabad³, Anna Esteve-Codina³, Antonia Ribes¹, Frederic Tort¹

¹Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic de Barcelona, IDIBAPS, CIBERER, Barcelona, Spain; ²Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany; ³CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology and Universitat Pompeu Fabra, Barcelona, Spain

Dynamics of NAD and glutathione metabolites in blood during aging, in disease and upon supplementation with NAD-booster

Liliya Euro^1,2, Kimmo Haimilahti¹, Sonja Jansson^1,2, Jana Buzkova^1,2, Anu Suomalainen-Wartiovaara^1,3

¹University of Helsinki, Finland; ²NADMED Ltd, Finland; ³HUS Diagnostic Centre, Finland

Enzymatic assay for UDP-GlcNAc and its application in the parallel assessment of substrate availability and protein O-GlcNAcylation

Marc Sunden^1,2, Divya Upadhyay^1,2, Rishi Banerjee^1,2, Nina Sipari³, Vineta Fellman^1,2,4, Jukka Kallijarvi^1,2, Janne Purhonen^1,2

¹Folkhalsan Research Center, Finland; ²Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Finland; ³Viikki Metabolomics Unit, University of Helsinki, Finland; ⁴Children’s Hospital, Helsinki University Hospital, Finland

Genetic testing for mitochondrial disease: The United Kingdom best practice guidelines

Eleni Mavraki^1,2, Robyn Labrum³, Kate Sergeant⁴, Charlotte L Alston^1,2, Cathy Woodward³, Conrad Smith⁴, Charlotte V Y Knowles^1,2, Yogen Patel³, Philip Hodsdon⁴, Jack P Baines^1,2, Emma L Blakely^1,2, James Polke³, Robert W Taylor^1,2, Carl Fratter⁴

¹NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; ²Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; ³Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; ⁴Oxford Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Identification of uncharacterized genes involved in mitochondrial OXPHOS function and integrity.

Marcos Javier Zamora Dorta, Sara Laine Menéndez, David Abia Holgado, Eduardo Balsa Martínez

Centro de Biología Molecular Severo Ochoa, Spain

Investigating the role of mito-nuclear genetic variation in determining m.3243A>G variant heteroplasmy

Alia K. Saeed¹, Róisín M. Boggan¹, Imogen G. Franklin¹, Charlotte L. Alston^1,2, Emma L. Blakely^1,2, Boriana Büchner³, Enrico Bugiardini⁴, Kevin Colclough⁵, Gráinne S. Gorman¹, Catherine Feeney¹, Michael G. Hanna⁴, Andrew T. Hattersley⁶, Thomas Klopstock^3,7,8, Cornelia Kornblum⁹, Michelangelo Mancuso¹⁰, Yi Shiau Ng¹, Kashyap A. Patel⁶, Robert D. S. Pitceathly⁴, Chiara Pizzamiglio⁴, Holger Prokisch^11,12, Jochen Schäfer¹³, Andrew M. Schaefer¹, Maggie H. Shepherd⁶, Annemarie Thaele¹⁴, Doug M. Turnbull¹, Cathy E. Woodward¹⁵, Heather J. Cordell¹⁶, Robert McFarland¹, Robert W. Taylor^1,2, Gavin H. Hudson¹, Sarah J. Pickett¹

¹Wellcome Centre for Mitochondrial Research and Institute for Translational and Clinical Research, Newcastle University, Newcastle upon Tyne, UK; ²NHS Highly Specialised Mitochondrial Diagnostic Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; ³Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-University (LMU Klinikum), Munich, Germany; ⁴Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; ⁵Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK; ⁶Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK; ⁷Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; ⁸German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; ⁹Department of Neurology, University Hospital Bonn, Bonn, Germany; ¹⁰Neurological Institute of Pisa, Italy; ¹¹Institute of Human Genetics, School of Medicine, Technische Universität München, München, Germany; ¹²Institute of Neurogenomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; ¹³Department of Neurology, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; ¹⁴Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany; ¹⁵Neurogenetics Unit, The National Hospital for Neurology and Neurosurgery, London, UK; ¹⁶Population Health Sciences Institute, Newcastle University, UK

Mitochondrial DNA depletion and deletion analysis using smMIPs

Maaike Brink^1,2, Sanne van Kraaij^1,2, Sanne Sweegers^1,2, Roel Smeets^1,2, Richard Rodenburg^1,2,3

¹Translational Metabolic Laboratory, Radboudumc, Nijmegen, The Netherlands; ²Radboud Center for Mitochondrial Medicine (RCMM), Radboudumc, Nijmegen, The Netherlands; ³Department of Pediatrics, Radboudumc, Nijmegen, The Netherlands

Ultrastructure of mitochondria in 3D from volume electron microscopy

Chenhao Wang^1,2, Leif Østergaard^3,4, Stine Hasselholt^3,4, Jon Sporring^1,2

¹Department of Computer Science, University of Copenhagen, Denmark; ²Center for Quantification of Imaging Data from MAX IV; ³Department of Clinical Medicine, Aarhus University, Denmark; ⁴Center of Functionally Integrative Neuroscience

Visualizing ATP dynamics in living mice

Masamichi Yamamoto, Jungmi Choi

National Cerebral and Cardiovascular Center, Japan

Applying sodium carbonate extraction mass spectrometry to investigate defects in the mitochondrial respiratory chain

David Robert Lindsay Robinson¹, Daniella Hock¹, Linden Muellner-Wong^1,2, Roopingsam Kugapreethan¹, Boris Reljic^1,3, Elliot Surgenor^3,4, Carlos Rodrigues^1,5, Nikeisha Caruana^1,6, David Stroud^1,2

¹Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; ²Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Australia; ³Department of Biochemistry and Molecular Biology, Monash University, Melbourne,Australia; ⁴The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; ⁵Baker Heart and Diabetes Institute, Melbourne, Australia; ⁶Institute for Health and Sport (IHES), Victoria University, Melbourne, Australia

Global analysis of protein methylation in the mitochondrial compartment of cancer cells: a proteomic approach

Ayusi Mondal^1,2, Alessandro Vai^1,2, Silvia Pedretti^1,3, Marianna Maniaci¹, Nico Mitro^1,3, Tiziana Bonaldi^1,4

¹Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS Milano, Italy; ²European School of Molecular Medicine (SEMM); ³Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; ⁴Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy

MITODIAG : The French network of diagnostic laboratories for mitochondrial diseases

Cécile Rouzier¹, Emmanuelle Pion², Céline Bris³, Patrizia Bonneau³, Valérie Desquiret³, Jean-Paul Bonnefont⁴, Pauline Gaignard⁵, Elise Lebigot⁵, Samira Ait-El-Mkadem Saadi¹, Sylvie Bannwarth¹, Konstantina Fragaki¹, Benoit Rucheton⁶, Marie-Laure Martin-Negrier⁷, Aurélien Trimouille⁷, Cécile Acquaviva-Bourdain⁸, Cécile Pagan⁸, Anne-Sophie Lebre⁹, Gaelle Hardy¹⁰, Stéphane Allouche¹¹, Pascal Reynier³, Mireille Cossee¹², Sharam Attarian¹³, Véronique Paquis-Flucklinger¹, Vincent Procaccio³

¹Service de génétique médicale, Centre de référence des maladies mitochondriales, CHU Nice, Université Cote d’Azur, CNRS, INSERM, IRCAN, Nice; ²Filnemus, laboratoire de génétique moléculaire, CHU Montpellier; ³Service de génétique, Institut de Biologie en santé, Centre National de référence Maladies Neurodégénératives et Mitochondriales, CHU Angers; ⁴Fédération de génétique médicale, Service de génétique moléculaire du GH Necker-enfants malades, Hôpital Necker-Enfants Malades, Paris; ⁵Laboratoire de Biochimie, Pôle BPP, CHU Paris Sud, Hôpital Bicêtre-le Kremlin Bicêtre, Paris; ⁶Pôle de biologie et pathologie, CHU Bordeaux; ⁷Unité fonctionnelle d’histologie moléculaire, Service de pathologie, CHU Bordeaux-GU Pellegrin, Bordeaux; ⁸Service de biochimie et biologie moléculaire Grand Est, UM Maladies Héréditaires du Métabolisme, Centre de biologie et pathologie Est, CHU Lyon HCL, GH Est, Lyon; ⁹Laboratoire de génétique, Hématologie et Immunologie, CHU Reims; ¹⁰Laboratoire de génétique moléculaire: maladies héréditaires et oncologie, Service de biochimie, biologie moléculaire et toxicologie environnementale, CHU Grenoble et des Alpes, Institut de biologie et pathologie, Grenoble; ¹¹Service de biochimie, Pôle Biologie, Pharmacie et Hygiène, CHU Caen, Hôpital de la Côte de Nacre, Caen; ¹²Laboratoire de Génétique Moléculaire, CHU Montpellier, PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier; ¹³Filnemus, Assistance Publique Hôpitaux Marseille, Service de Neurologie, Hôpital La Timone, Marseille

Multiomic mitochondrial and metabolic screening reveals potential biomarkers in inclusion body myositis

Judith Cantó Santos^1,2,3, Laura Valls Roca^1,2,3, Ester Tobías^1,2,3, Clara Oliva⁴, Francesc Josep García-García^1,2,3, Mariona Guitart Mampel^1,2,3, Félix Andújar Sánchez^1,2,3, Laia Farré Tarrats^1,2,3, Joan Padrosa^1,2,3, Raquel Aránega^1,2,3, Pedro J. Moreno Lozano^1,2,3, José César Milisenda^1,2,3, Rafael Artuch⁴, Josep M. Grau Junyent^1,2,3, Glòria Garrabou^1,2,3

¹Hereditary Metabolic Diseases and Muscular Diseases Lab, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; ²Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain; ³CIBERER— Spanish Biomedical Research Centre in Rare Diseases, Madrid, Spain; ⁴Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu; Esplugues de Llobregat, Barcelona, Spain

Network analysis of protein-protein interactions identifies intermediate filaments as a novel mitochondrial dynamics related structure

Irene M.G.M. Hemel, Carlijn Steen, Michiel Adriaens, Mike Gerards

Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, The Netherlands

Establishment of mitochondrial proline metabolic disorder patient-derived induced pluripotent stem cells as a new cellular model for aging associated disease study

Yu-Wen Huang, Tsung-Han Lee, Dar-Shong Lin

Mackay Memorial Hospital, Taiwan

Mitochondrial disorders unraveled by NGS technologies

Yulia Itkis¹, Tatiana Krylova¹, Natalia Pechatnikova², Ekaterina Zakharova¹

¹Research centre for medical genetics, Russian Federation; ²Morozov's Moscow City Child Clinical Hospital, Moscow, Russia

Incorporation of exogenous mitochondria into cells and their effects on the cells

Hisashi Ohta^1,2, Yosif El-Darawish^1,2, Masae Takeda^1,2, Takahiro Shibata^1,2, Keiichi Sakakibara^1,2, Rick Tsai¹, Masashi Suganuma¹

¹LUCA Science, Japan; ²Biological Drug Development based DDS technology, Hokkaido Univ.

Mitochondrial encapsulation technology for mitochondrial transplantation therapy

Yonghui Wang^1,2, Oliver Koivisto^1,2, Chang Liu^1,2, Hongbo Zhang^1,2

¹Pharmaceutical Sciences Laboratory, Åbo Akademi University, Finland; ²Turku Bioscience Centre, University of Turku and Åbo Akademi University

Inhibition of mtDNA transcription in liver reverses diet-induced obesity and hepatosteatosis in the mouse

Shan Jiang¹, Taolin Yuan¹, Laura Kremer¹, Florian Schober², Fynn Hansen², Diana Rubalcava-Gracia¹, Mara Mennuni¹, Roberta Filograna¹, David Alsina¹, Jelena Misic¹, Patrick Giavalisco³, Matthias Mann², Nils-Göran Larsson¹

¹Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden; ²Max-Planck Institute of Biochemistry, Martinsried, Germany; ³Metabolomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany

The mitochondrial phenotype of Leigh syndrome SURF1 mutant patient-derived fibroblasts and recovery using small molecules

Rachel M Hughes¹, Laura M Ellis¹, Naomi Hartopp¹, Emily Mossman¹, Gauri Bhosale², Annachiara Gandini², Alessandro Pristera², Christopher Doe², Scott P Allen¹, Oliver Bandmann¹, Laura Ferraiuolo¹, Pamela J Shaw¹, Heather J Mortiboys¹

¹Sheffield Institute for Translational Neuroscience, University of Sheffield, United Kingdom; ²Nanna Therapeutics, Cambridge, United Kingdom

Knockout of Complex III subunit Uqcrh decreases respiratory capacity and impairs cardiac contractile function independent of mitochondrial ROS production

Nadine Spielmann^1,9, Christina Schenkl^2,9, Tímea Komlódi^3,4, Patricia da Silva-Buttkus¹, Estelle Heyne², Jana Rohde¹, Oana V. Amarie¹, Birgit Rathkolb^1,5,6, Erich Gnaiger³, Torsten Doenst², Helmut Fuchs¹, Valérie Gailus-Durner¹, Martin Hrabě de Angelis^1,6,7,9, Marten Szibor^2,8,9

¹Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich, German Research Center for Environmental Health, Germany; ²Jena University Hospital, Friedrich-Schiller University of Jena, Germany; ³Oroboros Instruments, Innsbruck, Austria; ⁴Department of Biochemistry and Molecular Biology, Semmelweis University Budapest, Hungary; ⁵Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Germany; ⁶Member of German Center for Diabetes Research (DZD), Germany; ⁷Chair of Experimental Genetics Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München, Germany; ⁸BioMediTech & Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Finland; ⁹Contributed equally

Molecular insights into the role of complex V deficiency in heart development, function and disease

Mario Pavez-Giani^1,2, Karen an der Brügge¹, Till Stephan⁴, Felix Lange⁴, Jakob Fell^1,2, Alessandro Prigione³, Stefan Jakobs⁴, Lukas Cyganek^1,2

¹Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; ²German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany; ³Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; ⁴Research Group Mitochondrial Structure and Dynamics, Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany

Establishing mammalian cell models for research of NDUFS1-associated diseases

Lena Jentsch¹, Laura Schröter², Natascia Ventura^1,2

¹Heinrich Heine University Düsseldorf, Germany; ²IUF- Leibniz Research Institute for Environmental Medicine

A neuronal model of mtDNA disease reveals a compensatory reprogramming of the electron transfer chain during neuronal maturation

Shane Thomas Bell¹, Rebeca Acín-Pérez², Iffath Ghouri¹, Orian Shirihai², Robert Lightowlers¹, Oliver Russell¹

¹Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom; ²Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA, USA

Development of mutant mtDNA-targeted TALENs and their application to iPSC-based mitochondrial disease model.

Naoki Yahata, Ryuji Hata

Fujita Health University School of Medicine, Japan

Deficits in mitochondrial oxidative phosphorylation enhance SARS-CoV-2 replication

Yentli E. Soto Albrecht^1,2, Ryan Morrow¹, Arnold Olali¹, Devin Kenney^3,4, Prasanth Potluri¹, Deborah Murdock¹, Alessia Angelin¹, Florian Douam^3,4, Douglas C. Wallace^1,2

¹Children's Hospital of Philadelphia, USA; ²University of Pennsylvania, USA; ³Boston University, USA; ⁴National Emerging Infectious Diseases Laboratories, Boston, USA

Metabolic analysis of mouse sarcopenic skeletal muscle identifies new strategies to increase lifespan in C. elegans

Steffi M Jonk¹, Vicki Chrysostomou², James R Tribble¹, Jonathan G Crowston^2,3,4, Peter Swoboda¹, Pete A Williams¹

¹Karolinska Institutet, Sweden; ²Centre for Vision Research Duke-NUS & Singapore National Eye Centre, Singapore; ³Save Sight Institute at the University of Sydney, Australia; ⁴The University of Melbourne, Australia.

Delineating mitochondrial pathology using a genome-wide CRISPR/Cas9 activation screen

Yasmin Tang¹, Angela Pyle¹, Krutik Patel¹, Robert McFarland^1,2, Robert W. Taylor^1,2, Monika Oláhová¹

¹Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH; ²NHS Highly Specialised Rare Mitochondrial Disorders Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE2 4HH

Cancer and cellular senescence – two complementary stress models to study turnover and quality control of mitochondrial respiratory complexes.

Hanna Salmonowicz^1,2, Mahdi S Mahdi^1,2, Deepti Mudartha¹, Szymon Gorgon^1,2, Stadnik Dorota^1,2, Remigiusz Serwa^1,2, Karolina Szczepanowska^1,2

¹IMol Polish Academy of Sciences, Poland; ²ReMedy International Research Agenda

Proteotoxicity induced mitochondrial integrated stress response in CHCHD10-linked adult-onset spinal muscular atrophy

Sandra Harjuhaahto¹, Bowen Hu¹, Jouni Kvist¹, Fuping Zhang^2,3, Tomas Zárybnický², Kimmo Haimilahti⁴, Eija Pirinen⁴, Emilia Kuuluvainen², Ville Hietakangas^2,5, Satu Kuure^2,3, Manu Jokela^6,7, Emil Ylikallio^1,8, Henna Tyynismaa¹

¹Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki; ²Helsinki Institute of Life Science HiLIFE, University of Helsinki; ³Genetically Modified Rodents Unit, Laboratory Animal Center, University of Helsinki; ⁴Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki; ⁵Faculty of Biological and Environmental Sciences, University of Helsinki; ⁶Division of Clinical Neurosciences, Turku University Hospital and University of Turku; ⁷Department of Neurology, Neuromuscular Research Center, Tampere University Hospital and Tampere University; ⁸Clinical Neurosciences, Neurology, Helsinki University Hospital

Protective role of mitochondrial stress signaling and fragmentation in mitochondrial cardiomyopathy

Sofia Ahola, Lilli Pazurek, Fiona Mayer, Hendrik Nolte, Thomas Langer

Max Planck Institute for Biology of Ageing, Cologne, Germany

The Italian reappraisal on the most frequent genetic defects in hereditary optic neuropathies and the global top 10

Claudio Fiorini¹, Danara Ormanbekova¹, Flavia Palombo¹, Alberto Pasti¹, Michele Carbonelli², Giulia Amore², Martina Romagnoli², Pietro D'Agati², Maria Lucia Valentino^1,2, Piero Barboni³, Maria Lucia Cascavilla³, Anna Maria De Negri⁴, Federico Sadun⁵, Arturo Carta⁶, Francesco Testa⁷, Vittoria Petruzzella⁸, Silvana Guerriero⁸, Stefania Bianchi Marzoli⁹, Valerio Carelli^1,2, Chiara La Morgia^1,2, Leonardo Caporali²

¹IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; ²Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; ³Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy; ⁴Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy; ⁵Ospedale Oftalmico Roma, Rome, Italy; ⁶Ophthalmology Unit, University Hospital of Parma, Parma, Italy; ⁷Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; ⁸Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Bari, Italy; ⁹Neuroophthalmology Service and Ocular Electrophysiology laboratory, Department of Ophthalmology, IRCCS Istituto Auxologico Italiano, Milan, Italy

Aberrant ER-mitochondria communication in human mitochondrial disease

Eric A. Schon¹, Khushbu Kabra¹, Patricia Morcillo¹, Delfina Larrea¹, Estela Area-Gomez^1,2, Orhan Akman¹

¹Columbia University, USA; ²Centro de Investigaciones Biológicas “Margarita Salas”, Madrid, Spain

Mitochondrial F0F1-ATP synthase conditions the responsiveness of mitochondria to fission

Charlène Lhuissier¹, Julien Cassereau³, Valérie Desquiret-Dumas², Guy Lenaers¹, Naïg Gueguen², Arnaud Chevrollier¹

¹MITOVASC Université d'Angers, France; ²Departments of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France; ³Laboratoire de Neurobiologie et Neuropathologie, Centre Hospitalier Universitaire d'Angers, Angers, France

A screening method for mitochondrial disorders by high-resolution respirometry

Kersti Tepp¹, Kairit Joost², Natalja Timohhina¹, Marju Puurand¹, Tuuli Kaambre¹

¹National Institute of Chemical Physics and Biophysics, Estonia; ²Clinic of Internal Medicine, East-Tallinn Central Hospital, Estonia

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

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

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

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

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

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

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

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

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

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

Quantifying mitochondrial proteome remodeling during macrophage polarization

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

University of Lausanne, Switzerland

Mitochondrial injury in warm ischemia studied by high-resolution respirometry

Alba Timón-Gómez, Luiza HD Cardoso, Eleonora Baglivo, Carolina Doerrier, Erich Gnaiger

Oroboros Instruments GmBH, Austria

MitoCluster: integrated phenotyping and mouse model generation platform for mitochondrial disease and dysfunction

Micol Falabella¹, Patrick F. Chinnery², Laura C. Greaves³, Michael G. Hanna^1,4, Thomas M. Keane⁵, Robert McFarland³, Michal Minczuk², Owen J. Sansom^6,7, James B. Stewart³, Michelle Stewart⁸, Lydia Teboul⁸, Keira Turner², Jelle van den Ameele², Carlo Viscomi⁹, Sara Wells⁸, Alexander J. Whitworth², Robert D. S. Pitceathly^1,4

¹Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; ²Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge UK; ³Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, UK; ⁴NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; ⁵European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK; ⁶Cancer Research UK Beatson Institute, Glasgow, UK; ⁷Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; ⁸Mary Lyon Centre MRC Harwell, UK; ⁹University of Padua, Italy