线粒体ATP合成酶抑制因子1在细胞能量代谢中的调节作用  

Regulation of Mitochondrial ATP Synthase Inhibitor 1 in Cellular Energy Metabolism

作　　者：曹昕昱 章小英 叶建平 CAO Xinyu;ZHANG Xiaoying;YE Jianping(The Sixth People's Hospital affiliated to Shanghai Jiaotong University,Shanghai Diabetes Research Institute,Shanghai 200233,China)

机构地区：[1]上海交通大学附属第六人民医院,上海市糖尿病研究所,上海200233

出　　处：《中国细胞生物学学报》2020年第4期682-690,共9页Chinese Journal of Cell Biology

摘　　要：ATP除了为细胞提供能量外,还发挥重要的信号作用。因此,细胞内ATP水平的调节机制引起了越来越多的关注。ATP合成酶抑制因子(ATPase inhibitory factor 1,ATPIF1,简称IF1)是线粒体基质中的一个蛋白,其与呼吸链中的F1Fo-ATP合酶结合,调控后者合成和水解ATP的活性。该分子在肿瘤研究方面已有综述,但是在糖脂代谢领域还缺乏相关综述。该综述从能量代谢角度出发,阐明IF1分子在调节细胞ATP水平中的作用。IF1蛋白半衰期较短,其表达呈现组织特异性,活性受基因表达和蛋白修饰的双重调节。IF1活性在其质子化后或过表达条件下升高,使线粒体ATP合成减少,引起细胞能量代谢重新编程,糖酵解合成ATP增多,并且线粒体产生活性氧增加。这些作用可解释IF1促进癌细胞生长和提高细胞炎症反应的作用。相反,IF1活性在蛋白磷酸化后或基因敲除条件下降低,由此介导的代谢编程提高细胞对恶劣环境的适应能力,提高细胞的生存力,增加局部组织的抗炎能力。总之,IF1的这些作用为探索细胞内ATP水平调节机制和细胞能量代谢稳态机制提供了重要的指导意义。Intracellular ATP not only provides energy to cells,but also plays an important signaling role.Therefore,the regulation mechanism of intracellular ATP levels has attracted more and more attention.ATPIF1(ATPase inhibitory factor 1,IF1),is a mitochondrial protein that binds to the F1Fo-ATP synthase in the mitochondrial matrix to regulate the synthesis and hydrolysis of ATP.Although there are review articles on IF1 in the cancer biology field,the molecule has not been reviewed in the metabolism field of glucose and fatty acids.This review is prepared to summarize the latest information of IF1 with a focus on mitochondria to understand its role in the control of intracellular ATP level.With short half-life,IF1 is tissue-specifically expressed and primarily controlled by gene expression and protein modification.IF1 activity is upregulated after protonation or overexpression,which reduces mitochondrial ATP synthesis,causes reprogramming of cellular energy metabolism,increasing ATP production by glycolysis,and increasing mitochondria production of reactive oxygen species.These effects explain the role of IF1 in promoting cancer cell growth and increasing cellular inflammatory responses.In contrast,IF1 activity is reduced after protein phosphorylation or in gene knockout conditions,and this mediated metabolic programming increases the ability of cells to adapt to harsh environments,increases cell viability,and increases the anti-inflammatory capacity of local tissues.In conclusion,these roles of IF1 provide important guidance for exploring the regulation mechanism of ATP levels in cells and the homeostasis mechanism of cellular energy metabolism.

关 键 词：ATP合酶 ATP合成酶抑制因子1(IF1) 代谢重编程 线粒体低毒兴奋效应 活性氧 转基因小鼠 

分 类 号：Q25[生物学—细胞生物学]