Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies

Disease Models & Mechanisms

Roza Kucharczyk¹  Joanna Rytka¹  Lars M. Steinmetz²  Raeka S. Aiyar²  Agnès Rötig³  Déborah Tribouillard-Tanvier⁴  Marc Blondel⁴  Annie Glatigny⁵  Geneviève Dujardin⁵  Laras Pitayu⁶  Agnès Delahodde⁶  Vincent Procaccio⁷  Pascal Reynier⁷  Jean-Paul Lasserre⁸  Alain Dautant⁸  Jean-Paul di Rago⁸  Natalia Skoczen⁸ 

[1] Department of Genetics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland;European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany;Inserm U1163, Hôpital Necker-Enfants-Malades, Institut Imagine, Université Paris Descartes-Sorbonne Paris Cité, 149 rue de Sèvres, Paris 75015, France;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;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;Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Université Paris-Sud, rue Gregor Mendel, Orsay 91405, France;UMR CNRS 6214-INSERM U1083, Angers 49933, Cedex 9, France;University Bordeaux-CNRS, IBGC, UMR 5095, 1 rue Camille Saint-Saëns, Bordeaux F-33000, France;

关键词: OXPHOS;    Drug screening;    Genetic suppressors;    Mitochondrial disease;    Yeast;   

DOI  :  10.1242/dmm.020438

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown