Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA; Center for Structural Biology, Stony Brook University, Stony Brook, NY 11794, USA.
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA; Center for Structural Biology, Stony Brook University, Stony Brook, NY 11794, USA.
Mitochondrion. 2019 Nov;49:121-127. doi: 10.1016/j.mito.2019.07.012. Epub 2019 Aug 1.
Mitochondrial protein quality control requires the action of proteases to remove damaged or unnecessary proteins and perform key regulatory cleavage events. Important components of the quality control network are the mitochondrial AAA proteases, which capture energy from ATP hydrolysis to destabilize and degrade protein substrates on both sides of the inner membrane. Dysfunction of these proteases leads to the breakdown of mitochondrial proteostasis and is linked to the development of severe human diseases. In this review, we will describe recent insights into the structure and motions of the mitochondrial AAA proteases and related enzymes. Together, these studies have revealed the mechanics of ATP-driven protein destruction and significantly advanced our understanding of how these proteases maintain mitochondrial health.
线粒体蛋白质量控制需要蛋白酶的作用来去除受损或不必要的蛋白质，并执行关键的调节性切割事件。质量控制网络的重要组成部分是线粒体 AAA 蛋白酶，它利用 ATP 水解产生的能量来破坏和降解内膜两侧的蛋白质底物。这些蛋白酶的功能障碍导致线粒体蛋白质稳态的崩溃，并与严重人类疾病的发展有关。在这篇综述中，我们将描述最近对线粒体 AAA 蛋白酶和相关酶的结构和运动的深入了解。这些研究共同揭示了 ATP 驱动的蛋白质破坏的机制，并大大提高了我们对这些蛋白酶如何维持线粒体健康的理解。
