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Controlling quality and amount of mitochondria by mitophagy: insights into the role of ubiquitination and deubiquitination

机译:通过线粒体控制线粒体的质量和数量:泛素化和去泛素作用的见解

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Mitophagy is a selective autophagy pathway conserved in eukaryotes and plays an essential role in mitochondrial quality and quantity control. Mitochondrial fission and fusion cycles maintain a certain amount of healthy mitochondria and allow the isolation of damaged mitochondria for their elimination by mitophagy. Mitophagy can be classified into receptor-dependent and ubiquitin-dependent pathways. The mitochondrial outer membrane protein Atg32 is identified as the only known receptor for mitophagy in baker's yeast, whereas mitochondrial proteins FUNDC1, NIX/BNIP3L, BNIP3 and Bcl2L13 are recognized as mitophagy receptors in mammalian cells. Earlier studies showed that ubiquitination and deubiquitination occurs in yeast, yet there is no direct evidence for an ubiquitin-dependent mitophagy pathway in this organism. In contrast, a ubiquitin-/PINK1-/Parkin-dependent mitophagy pathway was unraveled and was extensively characterized in mammals in recent years. Recently, a quantitative method termed synthetic quantitative array (SQA) technology was developed to identify modulators of mitophagy in baker's yeast on a genome-wide level. The Ubp3-Bre5 deubiquitination complex was found as a negative regulator of mitophagy while promoting other autophagic pathways. Here we discuss how ubiquitination and deubiquitination regulates mitophagy and other selective forms of autophagy and what argues for using baker's yeast as a model to study the ubiquitin-dependent mitophagy pathway.
机译:线粒体吞噬是真核生物中保守的选择性自噬途径,在线粒体质量和数量控制中起着至关重要的作用。线粒体的分裂和融合周期维持一定量的健康线粒体,并允许分离受损的线粒体以通过线粒体消除。线粒体可以分为受体依赖性和泛素依赖性途径。线粒体外膜蛋白Atg32被确定为面包酵母中唯一的线粒体受体,而线粒体蛋白FUNDC1,NIX / BNIP3L,BNIP3和Bcl2L13被认为是哺乳动物细胞中的线粒体受体。较早的研究表明,酵母中会发生泛素化和去泛素化,但尚无直接证据表明这种生物中存在泛素依赖性线粒体途径。相反,近年来,泛素-/ PINK1- / Parkin依赖性线粒吞噬途径尚未阐明,并已在哺乳动物中得到广泛表征。最近,开发了一种称为合成定量阵列(SQA)技术的定量方法,以在全基因组水平上鉴定面包酵母中的线粒体调控因子。发现Ubp3-Bre5去泛素复合体是线粒体的负调节剂,同时促进其他自噬途径。在这里,我们讨论泛素化和去泛素化如何调节线粒体和其他自噬的选择性形式,以及为什么使用面包酵母作为模型来研究泛素依赖性线粒体途径。

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