Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
Int J Mol Sci. 2022 Nov 25;23(23):14725. doi: 10.3390/ijms232314725.
Mitochondria have many forms and can change their shape through fusion and fission of the outer and inner membranes, called "mitochondrial dynamics". Mitochondrial outer membrane proteins, such as mitochondrial fission protein 1 (FIS1), mitochondrial fission factor (MFF), mitochondrial 98 dynamics proteins of 49 kDa (MiD49), and mitochondrial dynamics proteins of 51 kDa (MiD51), can aggregate at the outer mitochondrial membrane and thus attract Dynamin-related protein 1 (DRP1) from the cytoplasm to the outer mitochondrial membrane, where DRP1 can perform a scissor-like function to cut a complete mitochondrion into two separate mitochondria. Other organelles can promote mitochondrial fission alongside mitochondria. FIS1 plays an important role in mitochondrial-lysosomal contacts, differentiating itself from other mitochondrial-fission-associated proteins. The contact between the two can also induce asymmetric mitochondrial fission. The kidney is a mitochondria-rich organ, requiring large amounts of mitochondria to produce energy for blood circulation and waste elimination. Pathological increases in mitochondrial fission can lead to kidney damage that can be ameliorated by suppressing their excessive fission. This article reviews the current knowledge on the key role of mitochondrial-fission-associated proteins in the pathogenesis of kidney injury and the role of their various post-translational modifications in activation or degradation of fission-associated proteins and targeted drug therapy.
线粒体具有多种形态，并可通过内外膜的融合和裂变来改变其形状，这一过程被称为“线粒体动力学”。线粒体的外膜蛋白，如线粒体裂变蛋白 1（FIS1）、线粒体裂变因子（MFF）、线粒体 49kDa 动力学蛋白（MiD49）和线粒体 51kDa 动力学蛋白（MiD51），可在其外膜上聚集，从而吸引细胞质中的动力相关蛋白 1（DRP1）向线粒体的外膜转移，DRP1 在那里可以发挥剪刀样的功能，将完整的线粒体切割成两个独立的线粒体。其他细胞器也可以与线粒体一起促进线粒体裂变。FIS1 在与溶酶体的线粒体接触中发挥着重要作用，使其与其他与线粒体裂变相关的蛋白质区分开来。两者的接触还可以诱导不对称的线粒体裂变。肾脏是一个富含线粒体的器官，需要大量的线粒体来为血液循环和废物清除提供能量。病理性的线粒体裂变增加会导致肾脏损伤，而通过抑制其过度裂变可以减轻这种损伤。本文综述了与线粒体裂变相关的蛋白在肾脏损伤发病机制中的关键作用，以及它们的各种翻译后修饰在裂变相关蛋白的激活或降解中的作用，以及靶向药物治疗。
