膜蛋白ATAD3A在线粒体质量控制中的作用

The Role of Membrane Protein ATAD3A in The Mitochondrial Quality Control

线粒体质量控制对于线粒体网络的稳态和线粒体功能的正常发挥具有重要意义。三磷酸腺苷酶家族蛋白3A(ATAD3A)是同时参与调节线粒体结构功能、线粒体动力学和线粒体自噬等重要生物学过程的线粒体膜蛋白之一。近期研究表明,ATAD3A既可与Mic60/Mitofilin和线粒体转录因子A(TFAM)等因子相互作用以维持线粒体嵴的形态和氧化磷酸化功能,又能与发动蛋白相关蛋白1(Drp1)结合而正性/负性调节线粒体分裂,还可作为线粒体外膜转位酶(TOM)复合物和线粒体内膜转位酶(TIM)复合物之间的桥接因子而介导PTEN诱导激酶(PINK1)输入线粒体进行加工,显示出促自噬或抗自噬活性。本文对ATAD3A在调控线粒体质量控制中的作用及其机制进行了综述。

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 PINK1-Parkin-dependent mitophagy.