Bordeaux University, 33000, Bordeaux, France; INSERM U1211, 33000, Bordeaux, France; CELLOMET, CGFB-146 Rue Léo Saignat, Bordeaux, France.
Bordeaux University, 33000, Bordeaux, France; INSERM U1211, 33000, Bordeaux, France.
Mol Aspects Med. 2020 Feb;71:100842. doi: 10.1016/j.mam.2019.100842. Epub 2020 Feb 3.
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.
线粒体是具有多种生物学功能的动态细胞器，负责能量转换、氧化还原信号转导、激素和维生素的生物合成、炎症或细胞死亡的执行等。细胞生物学研究表明，MITOCARTA 登记的 1158 个人类基因编码定位于线粒体的蛋白质。临床研究表明，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，这些线粒体蛋白中的许多可以在表达和功能上发生改变。因此，致病性线粒体遗传和功能缺陷参与了越来越多的罕见疾病的发病和进展。在这篇综述中，我们全面调查了生化、遗传和临床研究，这些研究证明了线粒体功能障碍与人类罕见疾病的关系。我们讨论了由线粒体功能障碍引起的症状的惊人多样性，以及提出的线粒体治疗策略，包括对正在进行的临床试验的调查。
