Veterans Affairs Maryland Health Center System, 10 North Greene Street, Baltimore, MD, 21201, USA.
Department of Anesthesiology and the Center for Shock, Trauma, and Anesthesiology Research (S.T.A.R.), School of Medicine, University of Maryland Baltimore, 685 W. Baltimore street, MSTF 534, Baltimore, 21201, MD, USA.
Transl Stroke Res. 2018 Jun;9(3):223-237. doi: 10.1007/s12975-017-0569-8. Epub 2017 Sep 21.
Mitochondria are complex organelles that undergo constant fusion and fission in order to adapt to the ever-changing cellular environment. The fusion/fission proteins, localized in the inner and outer mitochondrial membrane, play critical roles under pathological conditions such as acute brain injury and neurodegenerative diseases. Post-translational modifications of these proteins tightly regulate their function and activity, ultimately impacting mitochondrial dynamics and their efficiency to generate ATP. The individual post-translational modifications that are known to affect mitochondrial dynamics include SUMOylation, ubiquitination, phosphorylation, S-nitrosylation, acetylation, O-linked N-acetyl-glucosamine glycosylation, ADP-ribosylation, and proteolytic cleavage. Under stress or pathologic conditions, several of these modifications are activated leading to a complex regulatory mechanism that shifts the state of the mitochondrial network. The main goal is to accommodate and adapt the cellular bioenergetics metabolism to the energetic demand of the new extra- and/or intracellular environment. Understanding the complex relationship between these modifications on fusion and fission proteins in particular pathologic stress or diseases can provide new promising therapeutic targets and treatment approaches. Here, we discuss the specific post-translational modifications of mitochondrial fusion/fission proteins under pathologic conditions and their impact on mitochondrial dynamics.
线粒体是复杂的细胞器，为了适应不断变化的细胞环境，它们不断进行融合和裂变。定位于内外线粒体膜的融合/裂变蛋白在急性脑损伤和神经退行性疾病等病理条件下发挥着关键作用。这些蛋白质的翻译后修饰可紧密调节其功能和活性，最终影响线粒体动力学及其产生 ATP 的效率。已知影响线粒体动力学的个别翻译后修饰包括 SUMO 化、泛素化、磷酸化、S-亚硝基化、乙酰化、O-连接的 N-乙酰葡萄糖胺糖基化、ADP-核糖基化和蛋白水解切割。在应激或病理条件下，其中几种修饰被激活，导致一种复杂的调节机制，改变线粒体网络的状态。主要目标是适应细胞生物能量代谢以满足新的细胞内外环境的能量需求。了解特定病理应激或疾病下融合和裂变蛋白上这些修饰之间的复杂关系，可以为新的有前途的治疗靶点和治疗方法提供信息。在这里，我们讨论了病理条件下线粒体融合/裂变蛋白的特定翻译后修饰及其对线粒体动力学的影响。
