线粒体自噬紊乱在糖尿病肾病发病机制中的作用研究进展

Research progress in role of mitophagy dysfunction in pathogenesis of diabetic nephropathy

越来越多研究表明,线粒体自噬紊乱在糖尿病肾病(DN)的发病机制中起着重要作用。本综述介绍了哺乳动物中蛋白激酶PINK1和E3泛素连接酶Parkin(PINK1/Parkin)介导的线粒体自噬,并论述了其在DN发生时肾各细胞发生的紊乱以及相应的紊乱机制。其机制涉及线粒体形态动力学异常、细胞凋亡、氧化应激以及由于PINK1和Parkin表达降低所引起的线粒体自噬受抑制等。PINK1/Parkin介导的线粒体自噬能缓解自噬流受阻,清除受损的线粒体,减轻细胞内氧化应激状态,从而改善线粒体和细胞的形态结构和功能,最终在治疗DN中起重要作用,旨在为研究DN提供新的方向。

An increasing number of studies have shown that mitophagy disorder plays an impor?tant role in the pathogenesis of diabetic nephropathy(DN).In this review,we summarize the specific pathway of mitophagy induced by PINK1/Parkin and discuss the disorder of mitophagy in various kidney cells affected by DN,and the potential mechanisms involving abnormal mitochondrial morphology dynamics,apoptosis,oxidative stress and mitophagy dysfunction induced by decreased expressions of PINK and Parkin,which will cause changes in cells morphology and functional disruption and lead to DN.PINK and Parkin in kidney cells can relieve impaired autophagic flux,remove damaged mitochondria,decrease oxidative stress and ameliorate damaged structures and functions of mitochondria and cells,which can have a great impact on DN′s treatment.This review is expected to provide a new perspec?tive for the treatment of DN.