Mitochondrial quality control plays an important role in maintaining homeostasis of mitochondrial network and normal function of mitochondria.ATPase family AAA domain-containing protein 3A(ATAD3A)is one of the mitochondrial membrane proteins involved in the regulation of mitochondrial structure and function,mitochondrial dynamics,mitophagy and other important biological processes.Recent studies show that ATAD3A not only interacts with Mic60/Mitofilin and mitochondrial transcription factor A(TFAM)to maintain mitochondrial cristae morphology and oxidative phosphorylation,but also interacts with dynamin-related protein 1(Drp1)to positively/negatively regulate mitochondrial fission.In addition,ATAD3A serves as a bridging factor between the translocase of the outer mitochondrial membrane(TOM)complex and translocase of the inner mitochondrial membrane(TIM)complex to facilitate the import of PTEN-induced putative kinase protein 1(PINK1)into mitochondria and its processing displays a pro-autophagic or anti-autophagic activity.This article reviews the role and mechanism of ATAD3A in regulating mitochondrial quality control.Firstly,as an inner mitochondrial membrane protein,ATAD3A is involved in maintaining the stability of mitochondrial crista structure,and its gene deletion or mutation will cause the loss and breakage of crista.Secondly,ATAD3A is also involved in maintaining mitochondrial respiratory function and mitochondrial nucleoid homeostasis,and its gene deletion or mutation can reduce the activity of mitochondrial respiratory chain complex and enhance the size and movement of nucleoid.Thirdly,ATAD3A participates in the negative regulation of mitochondrial fusion,but its role in mitochondrial fission may dependent on specific cell types,as it can promote and/or inhibit the mitochondrial fission by increasing and/or decreasing phosphorylation or oligomerization of Drp1.Finally,ATAD3A can interact with mitophagy-related proteins(e.g.PINK1,autophagy/beclin-1 regulator 1(AMBRA1),acylglycerol kinase(AGK))to enhance/reduce PINK 1-Parkin-dependent mitophagy.
关键词
三磷酸腺苷酶家族蛋白3A/线粒体质量控制/线粒体结构/线粒体功能/线粒体动力学/自噬
Key words
ATPase family AAA domain-containing protein 3A/mitochondrial quality control/mitochondrial structure/mitochondrial function/mitochondrial dynamics/mitophagy
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