Mechanisms and Physiological Roles of Mitophagy in Yeast.
Mechanisms and Physiological Roles of Mitophagy in Yeast.
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DOI：
10.14348/molcells.2018.2214
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发表时间：
2018-01-31
影响因子：
3.8
通讯作者：
Kanki T
中科院分区：
文献类型：
--
作者：
Fukuda T;Kanki T
线粒体负责通过氧化磷酸化提供细胞的大部分能量。然而，线粒体也可能对细胞有害，因为它们是作为呼吸副产物产生的活性氧的主要来源。线粒体和细胞氧化损伤的积累导致多种病理。因此，维持健康和功能性线粒体的群体对于正常的细胞代谢是重要的。真核生物已经发展出防御机制来科普异常的线粒体。线粒体自噬（Mitochondria autophagy）被认为是这样一个过程，其选择性地将功能障碍或过量的线粒体隔离在双膜自噬体内，并将它们携带到溶酶体/空泡中进行降解。遗传学的力量和真核生物中基本细胞过程的保存使酵母成为理解线粒体自噬的一般机制、调节和功能的极好模型。在芽殖酵母中，线粒体表面蛋白Atg 32作为选择性自噬的线粒体受体，与Atg 11（选择性自噬类型的衔接蛋白）和Atg 8（定位于隔离膜的泛素样蛋白）相互作用。Atg 32在转录和转录后被调节以控制线粒体自噬。此外，由于Atg 32是线粒体自噬特异性蛋白，其缺陷突变体的分析，使调查的线粒体自噬的生理作用。在这里，我们回顾了最近的进展，在理解的分子机制和功能的重要性，线粒体自噬在酵母在多个层次。
Mitochondria are responsible for supplying of most of the cell’s energy via oxidative phosphorylation. However, mitochondria also can be deleterious for a cell because they are the primary source of reactive oxygen species, which are generated as a byproduct of respiration. Accumulation of mitochondrial and cellular oxidative damage leads to diverse pathologies. Thus, it is important to maintain a population of healthy and functional mitochondria for normal cellular metabolism. Eukaryotes have developed defense mechanisms to cope with aberrant mitochondria. Mitochondria autophagy (known as mitophagy) is thought to be one such process that selectively sequesters dysfunctional or excess mitochondria within double-membrane autophagosomes and carries them into lysosomes/vacuoles for degradation. The power of genetics and conservation of fundamental cellular processes among eukaryotes make yeast an excellent model for understanding the general mechanisms, regulation, and function of mitophagy. In budding yeast, a mitochondrial surface protein, Atg32, serves as a mitochondrial receptor for selective autophagy that interacts with Atg11, an adaptor protein for selective types of autophagy, and Atg8, a ubiquitin-like protein localized to the isolation membrane. Atg32 is regulated transcriptionally and post-translationally to control mitophagy. Moreover, because Atg32 is a mitophagy-specific protein, analysis of its deficient mutant enables investigation of the physiological roles of mitophagy. Here, we review recent progress in the understanding of the molecular mechanisms and functional importance of mitophagy in yeast at multiple levels.