title: Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies.
abstract: Mitochondrial diseases are severe and largely untreatable. Owing to the many essential processes carried out by mitochondria and the complex cellular systems that support these processes, these diseases are diverse, pleiotropic, and challenging to study. Much of our current understanding of mitochondrial function and dysfunction comes from studies in the baker's yeast Saccharomyces cerevisiae. Because of its good fermenting capacity, S. cerevisiae can survive mutations that inactivate oxidative phosphorylation, has the ability to tolerate the complete loss of mitochondrial DNA (a property referred to as 'petite-positivity'), and is amenable to mitochondrial and nuclear genome manipulation. These attributes make it an excellent model system for studying and resolving the molecular basis of numerous mitochondrial diseases. Here, we review the invaluable insights this model organism has yielded about diseases caused by mitochondrial dysfunction, which ranges from primary defects in oxidative phosphorylation to metabolic disorders, as well as dysfunctions in maintaining the genome or in the dynamics of mitochondria. Owing to the high level of functional conservation between yeast and human mitochondrial genes, several yeast species have been instrumental in revealing the molecular mechanisms of pathogenic human mitochondrial gene mutations. Importantly, such insights have pointed to potential therapeutic targets, as have genetic and chemical screens using yeast.
authors.affiliation: University Bordeaux-CNRS, IBGC, UMR 5095, 1 rue Camille Saint-Saëns, Bordeaux F-33000, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Lasserre
authors.affiliation: University Bordeaux-CNRS, IBGC, UMR 5095, 1 rue Camille Saint-Saëns, Bordeaux F-33000, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Dautant
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Raeka S
authors.initials: RS
authors.lastname: Aiyar
authors.affiliation: Department of Genetics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland.
authors.forename: Roza
authors.initials: R
authors.lastname: Kucharczyk
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Université Paris-Sud, 1 avenue de la terrasse, Gif-sur-Yvette 91198, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Glatigny
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR1078, Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, Etablissement Français du Sang (EFS) Bretagne, CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, Brest F-29200, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Tribouillard-Tanvier
authors.affiliation: Department of Genetics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rytka
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR1078, Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, Etablissement Français du Sang (EFS) Bretagne, CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, Brest F-29200, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Blondel
authors.affiliation: University Bordeaux-CNRS, IBGC, UMR 5095, 1 rue Camille Saint-Saëns, Bordeaux F-33000, France Department of Genetics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Skoczen
authors.affiliation: UMR CNRS 6214-INSERM U1083, Angers 49933, Cedex 9, France Département de Biochimie et Génétique, Centre Hospitalier Universitaire d'Angers, Angers 49933, Cedex 9, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Université Paris-Sud, rue Gregor Mendel, Orsay 91405, France.
authors.forename: Laras
authors.initials: L
authors.lastname: Pitayu
authors.affiliation: Inserm U1163, Hôpital Necker-Enfants-Malades, Institut Imagine, Université Paris Descartes-Sorbonne Paris Cité, 149 rue de Sèvres, Paris 75015, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Rötig
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Université Paris-Sud, rue Gregor Mendel, Orsay 91405, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Delahodde
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany Stanford Genome Technology Center, Department of Biochemistry, Stanford University, Palo Alto, CA 94304, USA Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5301, USA.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Université Paris-Sud, 1 avenue de la terrasse, Gif-sur-Yvette 91198, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Dujardin
authors.affiliation: UMR CNRS 6214-INSERM U1083, Angers 49933, Cedex 9, France Département de Biochimie et Génétique, Centre Hospitalier Universitaire d'Angers, Angers 49933, Cedex 9, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.affiliation: University Bordeaux-CNRS, IBGC, UMR 5095, 1 rue Camille Saint-Saëns, Bordeaux F-33000, France jp.dirago@ibgc.cnrs.fr.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: di Rago
mesh_terms: D000818:Animals; D004271:DNA, Fungal / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000628:therapy*; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D057170:Translational Research, Biomedical
chemical_list: D004271:DNA, Fungal
keywords: Drug screening; Genetic suppressors; Mitochondrial disease; OXPHOS; Yeast