Bingol Baris, Sheng Morgan
Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
Free Radic Biol Med. 2016 Nov;100:210-222. doi: 10.1016/j.freeradbiomed.2016.04.015. Epub 2016 Apr 16.
Mitochondrial quality control is central for maintaining a healthy population of mitochondria. Two Parkinson's disease genes, mitochondrial kinase PINK1 and ubiquitin ligase Parkin, degrade damaged mitochondria though mitophagy. In this pathway, PINK1 senses mitochondrial damage and activates Parkin by phosphorylating Parkin and ubiquitin. Activated Parkin then builds ubiquitin chains on damaged mitochondria to tag them for degradation in lysosomes. USP30 deubiquitinase acts as a brake on mitophagy by opposing Parkin-mediated ubiquitination. Human genetic data point to a role for mitophagy defects in neurodegenerative diseases. This review highlights the molecular mechanisms of the mitophagy pathway and the recent advances in the understanding of mitophagy in vivo.
线粒体质量控制对于维持健康的线粒体群体至关重要。两个帕金森病相关基因，即线粒体激酶PINK1和泛素连接酶Parkin，通过线粒体自噬降解受损的线粒体。在这一途径中，PINK1感知线粒体损伤，并通过磷酸化Parkin和泛素来激活Parkin。激活后的Parkin随后在受损线粒体上构建泛素链，将其标记以便在溶酶体中降解。USP30去泛素酶通过对抗Parkin介导的泛素化作用，对线粒体自噬起到制动作用。人类遗传学数据表明线粒体自噬缺陷在神经退行性疾病中发挥作用。本综述重点介绍了线粒体自噬途径的分子机制以及体内线粒体自噬研究的最新进展。
