Mitochondria are dynamic cellular organelles responsible for a large variety of biochemical processes as energy transduction, REDOX signaling, the biosynthesis of hormones and vitamins, inflammation or cell death execution. Cell biology studies established that 1158 human genes encode proteins localized to mitochondria, as registered in MITOCARTA. Clinical studies showed that a large number of these mitochondrial proteins can be altered in expression and function through genetic, epigenetic or biochemical mechanisms including the interaction with environmental toxics or iatrogenic medicine. As a result, pathogenic mitochondrial genetic and functional defects participate to the onset and the progression of a growing number of rare diseases. In this review we provide an exhaustive survey of the biochemical, genetic and clinical studies that demonstrated the implication of mitochondrial dysfunction in human rare diseases. We discuss the striking diversity of the symptoms caused by mitochondrial dysfunction and the strategies proposed for mitochondrial therapy, including a survey of ongoing clinical trials.

线粒体是动态细胞器，负责多种生化过程，例如能量转导，REDOX信号传导，激素和维生素的生物合成，炎症或细胞死亡。细胞生物学研究确定，在MITOCARTA中注册的1158个人类基因编码的蛋白质位于线粒体。临床研究表明，大量这些线粒体蛋白可通过遗传，表观遗传或生化机制（包括与环境毒物或医源性药物的相互作用）在表达和功能上发生改变。结果，致病性线粒体的遗传和功能缺陷参与了越来越多的罕见疾病的发作和发展。在这篇评论中，我们对生化进行了详尽的调查，遗传和临床研究表明线粒体功能障碍在人类罕见疾病中的意义。我们讨论了由线粒体功能障碍引起的症状的显着多样性以及为线粒体治疗提出的策略，包括正在进行的临床试验调查。