Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin, 130021, China.
Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin, 130021, China.
Eur J Cell Biol. 2021 Jan;100(1):151144. doi: 10.1016/j.ejcb.2020.151144. Epub 2020 Dec 7.
In response to mitochondrial damage, mitochondria activate mitochondrial dynamics to maintain normal functions, and an imbalance in mitochondrial dynamics triggers multiple programmed cell death processes. Recent studies have shown that phosphoglycerate mutase 5 (PGAM5) is associated with mitochondrial damage. PGAM5 activates mitochondrial biogenesis and mitophagy to promote a cellular compensatory response when mitochondria are mildly damaged, whereas severe damage to mitochondria leads to PGAM5 inducing excessive mitochondria fission, disruption to mitochondrial movement, and amplification of apoptosis, necroptosis and mitophagic death signals, which eventually evoke cell death. PGAM5 functions mainly through protein-protein interactions and specific Ser/Thr/His protein phosphatase activity. PGAM5 is also regulated by mitochondrial proteases. Detection of PGAM5 and its interacting protein partners should enable a more accurate evaluation of mitochondrial damage and a more precise method for the diagnosis and treatment of diseases.
针对线粒体损伤，线粒体激活线粒体动力学以维持正常功能，而线粒体动力学的失衡会触发多种程序性细胞死亡过程。最近的研究表明，磷酸甘油酸变位酶 5（PGAM5）与线粒体损伤有关。PGAM5 激活线粒体生物发生和线粒体自噬，以促进线粒体轻度损伤时的细胞代偿反应，而线粒体严重损伤则导致 PGAM5 诱导过度的线粒体分裂、破坏线粒体运动，并放大凋亡、坏死和噬亡性死亡信号，最终引发细胞死亡。PGAM5 的功能主要通过蛋白-蛋白相互作用和特定的 Ser/Thr/His 蛋白磷酸酶活性来实现。PGAM5 还受到线粒体蛋白酶的调节。检测 PGAM5 及其相互作用的蛋白伴侣，应该能够更准确地评估线粒体损伤，并更精确地诊断和治疗疾病。
