小分子泛素相关修饰物蛋白修饰对于发动蛋白相关蛋白1维持线粒体动力学平衡的影响  

Effect of SUMOylation on Maintaining Mitochondrial Dynamics Balance by DRP1

作　　者：张帅[1,3] 刘森 ZHANG Shuai;LIU Sen(Cooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province),School of Life and Health Sciences,Hubei University of Technology,Wuhan 430068,China;Key Laboratory of Fermentation Engineering(Ministry of Education),School of Life and Health Sciences,Hubei University of Technology,Wuhan 430068,China;Hubei WEL-SAFE Biotechnology Co.,Ltd.,Ezhou 436006,China)

机构地区：[1]湖北工业大学生命科学与健康工程学院,工业发酵省部共建协同创新中心,武汉430068 [2]湖北工业大学生命科学与健康工程学院,发酵工程教育部重点实验室,武汉430068 [3]湖北微生元生物科技有限公司,鄂州436006

出　　处：《生物化学与生物物理进展》2024年第8期1848-1859,共12页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(31971150);湖北省杰出青年基金(2019CFA069);工业发酵省部共建协同创新中心开放基金资助项目。

摘　　要：线粒体是细胞内能量代谢的中心,对于维持细胞稳态而言,其形态和功能的调控至关重要。小分子泛素相关修饰物蛋白(small ubiquitin-related modifier protein,SUMO)修饰和发动蛋白相关蛋白1(dynamin-related protein 1,DRP1)在细胞调控中扮演着重要角色,尤其与线粒体动力学密切相关。SUMO修饰是一种重要的蛋白质修饰形式,通过将靶蛋白与SUMO相连来调节这些蛋白质的功能。而DRP1是线粒体分裂蛋白,负责调节线粒体的形态和功能。近年来研究发现,SUMO修饰与DRP1之间存在复杂的相互作用网络,对于线粒体的分裂、融合、自噬等起着重要作用。在DRP1的可变结构域中,有8个赖氨酸残基可以在线粒体锚定蛋白连接酶(mitochondrial-anchored protein ligase,MAPL)的作用下完成SUMO修饰。并且不同亚型的SUMO蛋白对于DRP1功能的调节也不同。SUMO1修饰会使DRP1向线粒体富集,促进线粒体的分裂;SUMO2/3修饰会使DRP1向细胞质转移,减少线粒体的分裂。在实际的细胞程序中,不同亚型SUMO的修饰水平往往是由SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)的类型决定。线粒体作为细胞中重要的能量供应细胞器,其动力学的异常往往会导致诸多疾病的发生,例如:心肌缺血再灌注性损伤、阿尔茨海默病、脑血栓、视网膜病变等。本文综述了SUMO修饰与DRP1之间相互作用对于线粒体动力学调控的研究进展,为进一步揭示细胞调控机制和发展相关疾病的治疗策略提供一定的参考。Mitochondria,as the center of energy metabolism within the cell,play a crucial role in maintaining cell homeostasis.The regulation of its morphology and function is essential for the normal functioning of cells.In this complex regulatory network,the small ubiquitin-like modifier(SUMO)and dynamin-related protein 1(DRP1)have become the focus of research,especially their close association with mitochondrial dynamics.SUMOylation is an important form of protein modification that regulates the function of target proteins by binding them to SUMO.This modification also plays a significant role in mitochondrial dynamics.The complex network of interactions between SUMOylation and DRP1 plays a key role in mitochondrial division,fusion and autophagy.DRP1,as a mitochondrial fission protein,regulates the morphology and function of mitochondria with the participation of the endoplasmic reticulum(ER).Recent studies have revealed the complex relationship between DRP1 and SUMOylation.DRP1 completes SUMOylation under the action of mitochondrial-anchored protein ligase(MAPL).SUMOylation mainly occurs in the variable domain of DRP1,and eight lysine residues have been identified as its targets.DRP1 serves as the target protein of SUMO1 and SUMO2/3,which play different regulatory roles in mitochondrial fission.SUMO1 modification can enrich DRP1 into mitochondria,thus promoting mitochondrial fission.However,SUMO2/3 modification can transfer DRP1 to cytoplasm and reduce mitochondrial fission.This dynamic regulatory mechanism allows the cell to flexibly adjust the state of the mitochondria according to energy requirements.Correspondingly,there is also deSUMOylation.SUMO-specific proteases(SENPs)is responsible for the deSUMOylation of proteins,with seven subtypes identified so far.Among them,SENP3/5 is a SUMO2/3 specific deSUMOylation protease.In actual cellular processes,the SUMO1 and SUMO2/3 modifications of DRP1 occur simultaneously,which can be regarded as a competitive relationship between the them.So,the SUMOylation of DRP1 in cells

关 键 词：线粒体动力学 蛋白质翻译后修饰 小分子泛素相关修饰物蛋白修饰 发动蛋白相关蛋白1 线粒体分裂 

分 类 号：Q291[生物学—细胞生物学] R34[医药卫生—基础医学]