Mitochondria are essential organelles in eukaryotes. Most mitochondrial proteins are encoded by the nuclear genome and translated in the cytosol. Nuclear-encoded mitochondrial proteins need to be imported, processed, folded, and assembled into their functional states. To maintain protein homeostasis (proteostasis), mitochondria are equipped with a distinct set of quality control machineries. Deficiencies in such systems lead to mitochondrial dysfunction, which is a hallmark of aging and many human diseases, such as neurodegenerative diseases, cardiovascular diseases, and cancer. In this review, we discuss the unique challenges and solutions of proteostasis in mitochondria. The import machinery coordinates with mitochondrial proteases and chaperones to maintain the mitochondrial proteome. Moreover, mitochondrial proteostasis depends on cytosolic protein quality control mechanisms during crises. In turn, mitochondria facilitate cytosolic proteostasis. Increasing evidence suggests that enhancing mitochondrial proteostasis may hold therapeutic potential to protect against protein aggregation-associated cellular defects.

中文翻译：

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线粒体相关的蛋白质稳态。

线粒体是真核生物中必需的细胞器。大多数线粒体蛋白由核基因组编码并在细胞质中翻译。核编码的线粒体蛋白需要被导入、加工、折叠并组装成其功能状态。为了维持蛋白质稳态（蛋白质稳态），线粒体配备了一套独特的质量控制机制。这些系统的缺陷会导致线粒体功能障碍，这是衰老和许多人类疾病的标志，例如神经退行性疾病、心血管疾病和癌症。在这篇综述中，我们讨论了线粒体蛋白质稳态的独特挑战和解决方案。输入机制与线粒体蛋白酶和伴侣协调以维持线粒体蛋白质组。此外，线粒体蛋白质稳态取决于危机期间的胞质蛋白质质量控​​制机制。反过来，线粒体促进细胞质蛋白质稳态。越来越多的证据表明，增强线粒体蛋白质稳态可能具有预防蛋白质聚集相关细胞缺陷的治疗潜力。