ATPIF1

What is ATPIF1 protein?

ATPIF1 gene (ATP synthase inhibitory factor subunit 1) is a protein coding gene which situated on the short arm of chromosome 1 at locus 1p35. Enables several functions, including ATPase binding activity; angiostatin binding activity; and mitochondrial proton-transporting ATP synthase complex binding activity. Involved in several processes, including mitochondrial depolarization; negative regulation of ATPase activity; and regulation of protein targeting to mitochondrion. Located in cell surface and mitochondrion. The ATPIF1 protein is consisted of 105 amino acids and ATPIF1 molecular weight is approximately 12.2 kDa.

What is the function of ATPIF1 protein?

ATPIF1 or IF1 is the regulatory subunit of ATP synthase, which plays an inhibitory role in the function of ATP synthase. IF1 is mainly found in ATP synthase in mitochondria and bacteria, and it inhibits ATP hydrolase activity by binding to the catalytic subunit of ATP synthase, thereby preventing unnecessary hydrolysis of ATP when energy is sufficient. This inhibition helps to maintain the energy state of the cell and the ATP/ADP ratio, and can be removed when energy requirements increase to allow ATP synthase to synthesize ATP at a maximum rate.

ATPIF1 related signaling pathway

ATPIF1 protein is a protein that regulates mitochondrial ATP synthase activity. In heart tissue, increased expression of ATPIF1 is associated with pathological myocardial hypertrophy, and it inhibits ATP synthesis by promoting the formation of non-functional tetramers of ATP synthase, which in turn triggers the production of mitochondrial ROS. In the non-ischemic heart, the function of ATPIF1 reveals a key role of ATP synthase in the metabolic process of mitochondrial reprogramming. In addition, upregulation of ATPIF1 was associated with cardiometabolic reprogramming and pathological remodeling, and mice with cardio-specific ATPIF1 knockout were able to prevent metabolic switching and protect the heart from pathological remodeling under chronic stress.

ATPIF1 related diseases

ATPIF1 has been implicated in a variety of diseases and plays a key role in energy metabolism and cell survival. In tumorgenesis, ATPIF1 is involved in metabolic reprogramming of tumor cells by promoting aerobic glycolysis and regulating mitochondrial function. In addition, it is also involved in the cell's response to hypoxia and its role in cell differentiation. In heart tissue, upregulation of ATPIF1 is associated with increased myocardial metabolism and improved cardiac function. In neurodegenerative diseases, such as Alzheimer's disease, ATPIF1 may be associated with mitochondrial dysfunction.

Fig1. The potential involvement of IF1 in several diseases. (Emilia Gore, 2022)

Bioapplications of ATPIF1

It can be used to investigate the role of ATPIF1 in cellular energy metabolism and cell survival, especially the regulatory mechanisms in cardiometabolic and disease states. In addition, rhATPIF1 can be used to develop and test small molecule inhibitors targeting ATPIF1 that may be beneficial in treating related diseases. In biochemical and molecular biology research, rhATPIF1 contributes to understanding the regulatory mechanisms of ATP synthase and its role in cellular stress response. Although the current application of rhATPIF1 is mainly in the field of basic research, it provides an important foundation for future drug development and disease treatment.

Case Study 1: Bikash Manandhar, 2024

This study investigated if apoA-I enhances insulin secretion in β-cells by decreasing oxidative stress. Researchers treated Ins-1E cells with cholesterol and measured insulin secretion under different glucose conditions. Flow cytometry tracked apoA-I internalization by β-cells, and RNA sequencing assessed its impact on gene expression. Mass spectrometry identified an F1-ATPase β-subunit as a key apoA-I receptor on β-cells. Internalized apoA-I localized with mitochondria, reducing oxidative stress and boosting insulin secretion. The inhibitory factor IF1 reduced apoA-I internalization and increased oxidative stress. Gene expression differences in cells with internalized apoA-I pointed to effects on protein synthesis, unfolded protein response, insulin secretion, and mitochondrial function.

Fig1. Representative histograms of AF488 in the presence or absence of IF1.

Fig2. Control and cholesterol-loaded cells without or with IF1.

Case Study 2: Bo Zhou, 2022

In hearts with hypertrophy and failure, there's a shift to glucose metabolism, particularly glycolysis, which prioritizes biosynthesis over ATP production. The protein ATPIF1, which inhibits ATP synthase during ischemia, is upregulated in various models of pathological cardiac hypertrophy. The studies show that increased ATPIF1 leads to nonproductive ATP synthase tetramers, causing mitochondrial ROS production that stabilizes HIF1α and activates glycolysis. Mice with cardiac-specific ATPIF1 deletion resist this metabolic shift and are protected from pathological remodeling under chronic stress.

Fig3. ECAR analysis of cardiomyocytes with or without the addition of HIF1α inhibitor in the presence of ATPIF1.

Fig4. Immunoblot of ATPIF1 expression from liver or ventricular lysates.

ATPIF1 has several biochemical functions, for example, NOT 5-formyltetrahydrofolate cyclo-ligase activity,ATPase binding,ATPase inhibitor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by ATPIF1 itself. We selected most functions ATPIF1 had, and list some proteins which have the same functions with ATPIF1. You can find most of the proteins on our site.

ATPIF1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with ATPIF1 here. Most of them are supplied by our site. Hope this information will be useful for your research of ATPIF1.

PIK3CA;GSK3B;CHD3;hflC;tdk;pelY;opuD;yibD;UBQLN4;YAP1;BLK;Atp5a1