Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
CNRS, IBGC, UMR5095, 1 rue Camille Saint-Saëns, F-33000 Bordeaux, France; Université de Bordeaux, IBGC, UMR5095, 1 rue Camille Saint-Saëns, F-33000 Bordeaux, France.
Curr Biol. 2018 Feb 19;28(4):R170-R185. doi: 10.1016/j.cub.2018.01.004.
The maintenance of a healthy and functional mitochondrial network is critical during development as well as throughout life in the response to physiological adaptations and stress conditions. Owing to their role in energy production, mitochondria are exposed to high levels 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 the mitochondrial import of nuclear-encoded proteins. 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 levels. 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 could provide insights into the development of targeted treatments when these systems fail in disease.
维持健康和功能正常的线粒体网络对于发育以及生命过程中的生理适应和应激条件至关重要。由于线粒体在能量产生中发挥作用，因此它们容易受到高水平的活性氧的影响，使其特别容易受到线粒体 DNA 突变和蛋白质错误折叠的影响。鉴于线粒体是由核基因组和线粒体基因组编码的蛋白质组成的，因此协调蛋白质合成和核编码蛋白的线粒体导入具有内在的额外复杂性。出于这些原因，线粒体已经进化出多种质量控制系统，以确保存在必需数量的功能线粒体来满足细胞的需求。这些途径通过自噬作用消除受损的线粒体蛋白质或线粒体网络的部分，并通过生物发生添加蛋白质和脂质来更新组件，共同导致线粒体周转率。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。本文中，我们将讨论不同生理环境下的自噬作用，然后将其与其他质量控制途径联系起来，包括未折叠蛋白反应、囊泡脱落、蛋白酶解和泛素-蛋白酶体系统降解。了解这些途径如何有助于维持线粒体动态平衡，可以为这些系统在疾病中失效时针对特定疾病的治疗方法的开发提供思路。
