Department of Mitochondrial Proteostasis, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Cold Spring Harb Perspect Biol. 2019 Jul 1;11(7):a033936. doi: 10.1101/cshperspect.a033936.
Mitochondria are metabolic hubs that use multiple proteases to maintain proteostasis and to preserve their overall quality. A decline of mitochondrial proteolysis promotes cellular stress and may contribute to the aging process. Mitochondrial proteases have also emerged as tightly regulated enzymes required to support the remarkable mitochondrial plasticity necessary for metabolic adaptation in a number of physiological scenarios. Indeed, the mutation and dysfunction of several mitochondrial proteases can cause specific human diseases with severe metabolic phenotypes. Here, we present an overview of the proteolytic regulation of key mitochondrial functions such as respiration, lipid biosynthesis, and mitochondrial dynamics, all of which are required for metabolic control. We also pay attention to how mitochondrial proteases are acutely regulated in response to cellular stressors or changes in growth conditions, a greater understanding of which may one day uncover their therapeutic potential.
线粒体是代谢枢纽，它们使用多种蛋白酶来维持蛋白质稳态并保持整体质量。线粒体蛋白酶降解能力的下降会促进细胞应激，并可能导致衰老过程。线粒体蛋白酶也已成为受严格调控的酶，它们对于支持多种生理情况下代谢适应所需的显著线粒体可塑性是必需的。事实上，几种线粒体蛋白酶的突变和功能障碍会导致具有严重代谢表型的特定人类疾病。在这里，我们概述了关键线粒体功能（如呼吸、脂质生物合成和线粒体动力学）的蛋白水解调节，这些功能对于代谢控制都是必需的。我们还关注了线粒体蛋白酶如何在应对细胞应激或生长条件变化时被急性调节，对这方面的更深入了解可能有一天会揭示其治疗潜力。
