Lasserre Jean-Paul, Dautant Alain, Aiyar Raeka S, Kucharczyk Roza, Glatigny Annie, Tribouillard-Tanvier Déborah, Rytka Joanna, Blondel Marc, Skoczen Natalia, Reynier Pascal, Pitayu Laras, Rötig Agnès, Delahodde Agnès, Steinmetz Lars M, Dujardin Geneviève, Procaccio Vincent, di Rago Jean-Paul
University Bordeaux-CNRS, IBGC, UMR 5095, 1 rue Camille Saint-Saëns, Bordeaux F-33000, France.
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
Dis Model Mech. 2015 Jun;8(6):509-26. doi: 10.1242/dmm.020438.
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.
线粒体疾病严重且大多无法治愈。由于线粒体执行的众多基本过程以及支持这些过程的复杂细胞系统，这些疾病具有多样性、多效性，且研究颇具挑战性。我们目前对线粒体功能和功能障碍的许多理解都来自对酿酒酵母的研究。由于其良好的发酵能力，酿酒酵母能够在使氧化磷酸化失活的突变中存活，有能力耐受线粒体DNA的完全缺失（这种特性称为“小菌落阳性”），并且易于进行线粒体和核基因组操作。这些特性使其成为研究和解析众多线粒体疾病分子基础的优秀模型系统。在此，我们回顾了这种模式生物对线粒体功能障碍所引发疾病产生的宝贵见解，这些疾病范围从氧化磷酸化的原发性缺陷到代谢紊乱，以及线粒体基因组维持或动态变化方面的功能障碍。由于酵母和人类线粒体基因之间高度的功能保守性，几种酵母物种在揭示人类致病性线粒体基因突变的分子机制方面发挥了重要作用。重要的是，这些见解指出了潜在的治疗靶点正如利用酵母进行的遗传和化学筛选所表明的那样。
