Autophagy accounts for approximately one-third of mitochondrial protein turnover and is protein selective.
Autophagy accounts for approximately one-third of mitochondrial protein turnover and is protein selective.
复制标题
自噬约占线粒体蛋白质更新的三分之一，并且具有蛋白质选择性。
DOI：
10.1080/15548627.2019.1586258
复制
发表时间：
2019
期刊：
影响因子：
13.3
通讯作者：
Pallanck,LeoJ
中科院分区：
文献类型：
--
作者：
Vincow,EvelynS;Thomas,RuthE;Merrihew,GenniferE;Shulman,NicholasJ;Bammler,TheoK;MacDonald,JamesW;MacCoss,MichaelJ;Pallanck,LeoJ
The destruction of mitochondria through macroautophagy (autophagy) has been recognised as a major route of mitochondrial protein degradation since its discovery more than 50 years ago, but fundamental questions remain unanswered. First, how much mitochondrial protein turnover occurs through auto-phagy? Mitochondrial proteins are also degraded by nonautophagic mechanisms, and the proportion of mitochondrial protein turnover that occurs through autophagy is still unknown. Second, does auto-phagy degrade mitochondrial proteins uniformly or selectively? Autophagy was originally thought to degrade all mitochondrial proteins at the same rate, but recent work suggests that mitochondrial autophagy may be protein selective. To investigate these questions, we used a proteomics-based approach in the fruit flyDrosophila melanogaster, comparing mitochondrial protein turnover rates in autophagy-deficientAtg7mutants and controls. We found that ~35% of mitochondrial protein turnover occurred via autophagy. Similar analyses usingparkinmutants revealed that parkin-dependent mitophagy accounted for ~25% of mitochondrial protein turnover, suggesting that most mitochondrial autophagy specifically eliminates dysfunctional mitochondria. We also found that our results were incompatible with uniform autophagic turnover of mitochondrial proteins and consistent with protein-selective autophagy. In particular, the autophagic turnover rates of individual mitochondrial proteins varied widely, and only a small amount of the variation could be attributed to tissue differences in mitochondrial composition and autophagy rate. Furthermore, analyses comparing autophagy-deficient and control human fibroblasts revealed diverse autophagy-dependent turnover rates even in homogeneous cells. In summary, our work indicates that autophagy acts selectively on mitochondrial proteins, and that most mitochondrial protein turnover occurs through non-autophagic processes.Abbreviations:Atg5: Autophagy-related 5(Drosophila); ATG5: autophagy related 5(human);Atg7: Autophagy-related 7(Drosophila); ATG7: autophagy related 7(human); DNA: deoxyribonucleic acid; ER: endoplasmic reticulum; GFP: green fluorescent protein; MS: mass spectrometry;park: parkin(Drosophila); Pink1: PTEN-induced putative kinase 1(Drosophila); PINK1: PTEN-induced kinase 1(human);PRKN: parkin RBR E3 ubiquitin protein ligase(human); RNA: ribonucleic acid; SD: standard deviation; Ub: ubiquitin/ubiquitinated; WT: wild-type;YME1L: YME1 like ATPase(Drosophila); YME1L1: YME1 like 1 ATPase(human)
