Maintaining cellular protein homeostasis (proteostasis) is an essential task for all eukaryotes. Proteostasis failure worsens with aging and is considered a cause of and a therapeutic target for age-related diseases including neurodegenerative disorders. The cellular networks regulating proteostasis and the pathogenic events driving proteostasis failure in disease remain poorly understood. Model organism studies in yeast and Drosophila reveal an intriguing link between mitochondrial function and proteostasis. In this review we examine recent findings on mitochondrial outer membrane (MOM)-associated mRNA translation, how this process is sensitive to mitochondrial dysfunction and constantly surveyed by ribosome-associated quality control (RQC), and how defects in this process generate aberrant proteins with unusual C-terminal extensions (CTEs) that promote aggregation and drive proteostasis failure. We also discuss the implications for human diseases.

维持细胞蛋白质稳态（蛋白稳态）是所有真核生物的基本任务。蛋白质变性失败随着年龄的增长而加剧，被认为是与年龄有关的疾病（包括神经退行性疾病）的原因和治疗目标。调节蛋白稳态和驱动疾病中蛋白稳态失败的致病事件的细胞网络仍然知之甚少。酵母和果蝇中的模型生物研究揭示了线粒体功能与蛋白稳态之间的有趣联系。在这篇综述中，我们检查了有关线粒体外膜（MOM）相关mRNA翻译的最新发现，该过程如何对线粒体功能障碍敏感并通过核糖体相关质量控制（RQC）不断进行调查，以及该过程中的缺陷如何导致异常蛋白的产生。不寻常的C端扩展（CTE），可促进聚集并驱动蛋白稳态失败。我们还将讨论对人类疾病的影响。