线粒体ATP合酶抑制因子1在线粒体稳态中的调节作用

The Regulatory Role of Mitochondrial ATP Synthase Inhibitor 1in Mitochondrial Homeostasis

线粒体作为细胞的重要能量来源,其数量、质量及功能的稳定对维持细胞的正常活动至关重要,且其稳态的调节依赖于线粒体质量控制系统(包括线粒体自噬、线粒体融合/分裂及线粒体生物合成等)。线粒体蛋白ATP合酶抑制因子1(ATP synthase inhibitor 1,IF1)是线粒体基质中抑制F1FoATP酶/合酶活性的天然小分子蛋白质。在细胞缺氧缺血等特殊生理情况下,IF1通过改变自身的聚合状态,抑制F1FoATP酶水解ATP的活性,从而抑制细胞内的ATP被过度水解。最近的研究证实,IF1的抑制作用是双向的,其即可抑制F1FoATP酶活性,又可抑制F1FoATP合酶活性。因此,IF1可通过靶向F1FoATP酶/合酶活性及相关信号通路,参与调节线粒体质量,维持线粒体稳态。该文综述IF1在线粒体质量控制中的相关调节机制,包括IF1维持线粒体氧化还原平衡、IF1介导线粒体自噬、IF1促进线粒体融合/分裂三条通路,以及三者之间相互作用的关系,为探索IF1在相关疾病的发生、发展及治疗中的作用提供理论参考。

Mitochondrion is an important energy source for cells,the stability of its quantity,quality and function is essential to maintain the normal activities of cells.The regulation of mitochondrial homeostasis depends on mitochondrial quality control systems,including mitophagy,mitochondrial fusion/fission,and mitochondrial biosynthesis and so on.Mitochondrial protein IF1(ATP synthase inhibitor 1)is a natural small molecule protein that inhibits the activity of F1FoATPase/synthase in the mitochondrial matrix.In the polymerization state,it exerts the activity of inhibiting the hydrolysis of ATP by F1FoATPase,thereby inhibiting the excessive hydrolysis of ATP in cells and maintaining cell survival.Recent studies have also confirmed that IF1 inhibition is bidirectional,that is,it can inhibit the activity of both F1FoATPase and F1FoATP synthase.Hence,IF1 can regulate mitochondrial quality and maintain mitochondrial homeostasis by targeting F1FoATP enzyme/synthase activity and related signal pathways.This article reviews the regulation mechanism of IF1 in mitochondrial quality control,regarding mitochondrial redox balance,mitophagy,and mitochondrial fusion/division,and the interaction among them,so as to provide theoretical reference for exploring the role of IF1 in the occurrence,development and treatment of related diseases.