Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance.
Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance.
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线粒体维护中的线粒体和质量控制机制。
DOI：
10.1016/j.cub.2018.01.004
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发表时间：
2018-02-19
期刊：
影响因子：
--
通讯作者：
Youle RJ
中科院分区：
文献类型：
--
作者：
Pickles S;Vigié P;Youle RJ
维持健康和功能性的线粒体网络在发育期间以及整个生命中对生理适应和科普压力至关重要。由于线粒体在能量生产中的作用，它们暴露于大量的活性氧，使它们特别容易受到线粒体DNA突变和蛋白质错误折叠的影响。鉴于线粒体是由核和线粒体基因组编码的蛋白质形成的，蛋白质合成和核编码蛋白质输入的协调中固有的额外的复杂性层。由于这些原因，线粒体已经进化出多种质量控制系统，以确保存在必要数量的功能性线粒体以满足细胞的需求。这些途径通过线粒体自噬消除受损的线粒体蛋白或线粒体网络的部分，并通过生物合成添加蛋白质和脂质来更新组分，共同导致线粒体周转。线粒体质量控制机制是多层次的，在蛋白质、细胞器和细胞水平上运作。在此，我们讨论了线粒体自噬在不同的生理背景下，然后将其与其他质量控制途径，包括未折叠的蛋白质反应，脱落的囊泡，蛋白水解和降解的泛素-蛋白酶体系统。了解这些途径如何有助于维持线粒体稳态可能会导致在这些系统在疾病中失败时开发靶向治疗的见解。
The maintenance of a healthy and functional mitochondrial network is critical during development as well as throughout life to respond to physiological adaptations and to cope with stress. Owing to their role in energy production, mitochondria are exposed to high amounts of reactive oxygen species making them particularly vulnerable to mitochondrial DNA mutations and protein misfolding. Given that mitochondria are formed from proteins encoded by both nuclear and mitochondrial genomes, an additional layer of complexity is inherent in the coordination of protein synthesis and nuclear encoded protein import. For these reasons mitochondria have evolved multiple systems of quality control to ensure that the requisite number of functional mitochondria are present to meet the demands of the cell. These pathways work to eliminate damaged mitochondrial proteins or parts of the mitochondrial network by mitophagy and renew components by adding protein and lipids through biogenesis, collectively resulting in mitochondrial turnover. Mitochondrial quality control mechanisms are multi-tiered, operating at the protein, organelle and cell level. Herein, we discuss mitophagy in different physiological contexts and then relate it to other quality control pathways including the unfolded protein response, shedding of vesicles, proteolysis and degradation by the ubiquitin-proteasome system. Understanding how these pathways contribute to the maintenance of mitochondrial homeostasis may lead to insights in the development of targeted treatments when these systems fail in disease.
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DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
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影响因子：
16.6
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DOI：
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发表时间：
2016-08-08
期刊：
Current biology : CB
影响因子：
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通讯作者：
Haynes CM