Regulation of Mitochondrial ATP Synthase Inhibitor 1 in Cellular Energy Metabolism

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 antiinflammatory 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.

CSTR: 32200.14.cjcb.2020.04.0016