Common Principles and Specific Mechanisms of Mitophagy from Yeast to Humans.
Common Principles and Specific Mechanisms of Mitophagy from Yeast to Humans.
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DOI：
10.3390/ijms22094363
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发表时间：
2021-04-22
影响因子：
5.6
通讯作者：
Reichert AS
中科院分区：
文献类型：
--
作者：
Kumar R;Reichert AS
线粒体是真核细胞中的双膜结合细胞器，对多种细胞功能至关重要，包括能量转换和 ATP 产生、铁硫生物发生、脂质和氨基酸代谢以及调节细胞凋亡和应激反应。线粒体功能障碍在机制上与多种神经退行性疾病、癌症和衰老有关。过多和功能失调/受损的线粒体会被称为线粒体自噬的选择性自噬途径降解。芽殖酵母和哺乳动物都使用核心自噬相关基因（ATG）的保守机制来执行和调节线粒体自噬。在哺乳动物细胞中，PINK1-PARKIN 线粒体自噬途径是一种经过充分研究的途径，可感知功能失调的线粒体并标记它们在溶酶体中降解。 PINK1-PARKIN 介导的线粒体自噬依赖于非 ATG 蛋白的泛素结合线粒体自噬接头。 PINK1 和 PARKIN 的功能丧失突变与人类帕金森病 (PD) 相关，并且线粒体自噬缺陷被认为是主要的病理机制。尽管人们普遍认为酵母细胞缺乏 PINK1 和 PARKIN 同源物，并且酵母中的线粒体自噬仅受受体介导的线粒体自噬调节，但一些研究表明，泛素化依赖性线粒体自噬途径也存在。在这里，我们将讨论哺乳动物和酵母之间的共同机制，后者的线粒体自噬如何以泛素依赖和不依赖的方式进行调节，以及为什么这些途径对于酵母细胞在各种生理应激条件下的生存和适应至关重要。
Mitochondria are double membrane-bound organelles in eukaryotic cells essential to a variety of cellular functions including energy conversion and ATP production, iron-sulfur biogenesis, lipid and amino acid metabolism, and regulating apoptosis and stress responses. Mitochondrial dysfunction is mechanistically linked to several neurodegenerative diseases, cancer, and ageing. Excessive and dysfunctional/damaged mitochondria are degraded by selective autophagic pathways known as mitophagy. Both budding yeast and mammals use the well-conserved machinery of core autophagy-related genes (ATGs) to execute and regulate mitophagy. In mammalian cells, the PINK1-PARKIN mitophagy pathway is a well-studied pathway that senses dysfunctional mitochondria and marks them for degradation in the lysosome. PINK1-PARKIN mediated mitophagy relies on ubiquitin-binding mitophagy adaptors that are non-ATG proteins. Loss-of-function mutations in PINK1 and PARKIN are linked to Parkinson´s disease (PD) in humans, and defective mitophagy is proposed to be a main pathomechanism. Despite the common view that yeast cells lack PINK1- and PARKIN-homologs and that mitophagy in yeast is solely regulated by receptor-mediated mitophagy, some studies suggest that a ubiquitination-dependent mitophagy pathway also exists. Here, we will discuss shared mechanisms between mammals and yeast, how mitophagy in the latter is regulated in a ubiquitin-dependent and -independent manner, and why these pathways are essential for yeast cell survival and fitness under various physiological stress conditions.
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DOI：
10.1083/jcb.3.3.349
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
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影响因子：
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