Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
Cold Spring Harb Perspect Biol. 2019 Jun 3;11(6):a033944. doi: 10.1101/cshperspect.a033944.
The mitochondrial proteome encompasses more than a thousand proteins, which are encoded by the mitochondrial and nuclear genomes. Mitochondrial biogenesis and network health relies on maintenance of protein import pathways and the protein-folding environment. Cell-extrinsic or -intrinsic stressors that challenge mitochondrial proteostasis negatively affect organellar function. During conditions of stress, cells use impaired protein import as a sensor for mitochondrial dysfunction to activate a stress response called the mitochondrial unfolded protein response (UPR). UPR activation leads to an adaptive transcriptional program that promotes mitochondrial recovery, metabolic adaptations, and innate immunity. In this review, we discuss the regulation of UPR activation as well as its role in maintaining mitochondrial homeostasis in physiological and pathological scenarios.
线粒体蛋白质组包含一千多种蛋白质，这些蛋白质由线粒体和核基因组编码。线粒体的生物发生和网络健康依赖于蛋白质输入途径和蛋白质折叠环境的维持。挑战线粒体蛋白质稳态的细胞外在或内在应激因子会对细胞器功能产生负面影响。在应激条件下，细胞将受损的蛋白质输入作为线粒体功能障碍的传感器，激活一种称为线粒体未折叠蛋白反应 (UPR) 的应激反应。UPR 的激活导致适应性转录程序的激活，从而促进线粒体的恢复、代谢适应和先天免疫。在这篇综述中，我们讨论了 UPR 激活的调节及其在生理和病理情况下维持线粒体动态平衡中的作用。
