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

LING Junhe¹, TIAN Xinyuan^2,3, CHEN Xiaohua⁴, HUANG Guomin⁴, WANG Yupei^2,3*, HUI Ling^2,3*

( ¹School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, China; ² Center for Medical Genetics, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou 730050, China; ³ Medical Genetics Center, Gansu Provincial Central Hospital, Lanzhou 730050, China; ⁴ Institute of Modern Physics, University of Chinese Academy of Sciences, Lanzhou 730000, China)

Abstract:

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.

CSTR: 32200.14.cjcb.2022.12.0009