Mitochondria serve as a hub for many cellular processes, including bioenergetics, metabolism, cellular signaling, redox balance, calcium homeostasis, and cell death. The mitochondrial proteome includes over a thousand proteins, encoded by both the mitochondrial and nuclear genomes. The majority (~99%) of proteins are nuclear encoded that are synthesized in the cytosol and subsequently imported into the mitochondria. Within the mitochondria, polypeptides fold and assemble into their native functional form. Mitochondria health and integrity depend on correct protein import, folding, and regulated turnover termed as mitochondrial protein quality control (MPQC). Failure to maintain these processes can cause mitochondrial dysfunction that leads to various pathophysiological outcomes and the commencement of diseases. Here, we summarize the current knowledge about the role of different MPQC regulatory systems such as mitochondrial chaperones, proteases, the ubiquitin-proteasome system, mitochondrial unfolded protein response, mitophagy, and mitochondria-derived vesicles in the maintenance of mitochondrial proteome and health. The proper understanding of mitochondrial protein quality control mechanisms will provide relevant insights to treat multiple human diseases.

中文翻译：

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线粒体蛋白质量控制机制

线粒体是许多细胞过程的枢纽，包括生物能量学、新陈代谢、细胞信号、氧化还原平衡、钙稳态和细胞死亡。线粒体蛋白质组包括超过一千种蛋白质，由线粒体和核基因组编码。大多数 (~99%) 的蛋白质是核编码的，在细胞质中合成，随后输入到线粒体中。在线粒体内，多肽折叠并组装成它们的天然功能形式。线粒体的健康和完整性取决于正确的蛋白质导入、折叠和调节的周转，称为线粒体蛋白质质量控​​制 (MPQC)。未能维持这些过程会导致线粒体功能障碍，从而导致各种病理生理结果和疾病的开始。这里，我们总结了当前关于不同 MPQC 调节系统作用的知识，例如线粒体伴侣蛋白、蛋白酶、泛素-蛋白酶体系统、线粒体未折叠蛋白反应、线粒体自噬和线粒体衍生的囊泡在维持线粒体蛋白质组和健康方面的作用。对线粒体蛋白质质量控​​制机制的正确理解将为治疗多种人类疾病提供相关见解。