ATPase Inhibitory Factor 1 (IF1) is a mitochondrial protein that plays a crucial role in regulating the activity of ATP synthase, an enzyme responsible for ATP production in cells. ATP synthase operates in the mitochondria, converting ADP and inorganic phosphate into ATP, the primary energy currency of the cell. IF1 inhibits the ATP hydrolysis activity of ATP synthase, thereby preventing the wasteful consumption of ATP under conditions where the mitochondrial membrane potential is compromised .
IF1 is a basic amphiphilic protein composed of 81 amino acids. It is highly conserved across various species, indicating its essential role in cellular metabolism . The primary function of IF1 is to inhibit the ATP hydrolysis activity of the F1-ATPase component of ATP synthase. This inhibition is particularly important during ischemic conditions or other metabolic stresses where the mitochondrial membrane potential drops, and ATP synthase could potentially reverse its function to hydrolyze ATP instead of synthesizing it .
IF1 is expressed in various tissues, with higher expression levels observed in tissues with high metabolic rates, such as the heart, liver, and brain. The regulation of IF1 expression is complex and involves both transcriptional and post-transcriptional mechanisms. Recent studies have shown that IF1 is overexpressed in several types of human cancers, including colon, lung, breast, and ovarian cancers . This overexpression is associated with the promotion of aerobic glycolysis and reactive oxygen species (ROS) signaling, which enhances cell proliferation and survival .
The overexpression of IF1 in cancer cells has significant clinical implications. It has been suggested that IF1 could serve as a predictive marker for clinical outcomes in cancer patients. Additionally, targeting IF1 could be a potential therapeutic strategy for cancer treatment, as its inhibition could disrupt the metabolic reprogramming that supports cancer cell growth and survival .
Recombinant human IF1 is produced using Escherichia coli expression systems. The recombinant protein is typically purified to high levels of purity (>95%) and is used in various research applications, including studies on mitochondrial function, cancer metabolism, and the development of potential therapeutic interventions .