Abstract
IF1 is an endogenous inhibitor protein of mitochondrial ATP synthase. It is evolutionarily conserved throughout all eukaryotes and it has been proposed to play crucial roles in prevention of the wasteful reverse reaction of ATP synthase, in the metabolic shift from oxidative phosphorylation to glycolysis, in the suppression of ROS (reactive oxygen species) generation, in mitochondria morphology and in haem biosynthesis in mitochondria, which leads to anaemia. Here, we report the phenotype of a mouse strain in which IF1 gene was destroyed. Unexpectedly, individuals of this IF1-KO (knockout) mouse strain grew and bred without defect. The general behaviours, blood test results and responses to starvation of the IF1-KO mice were apparently normal. There were no abnormalities in the tissue anatomy or the autophagy. Mitochondria of the IF1-KO mice were normal in morphology, in the content of ATP synthase molecules and in ATP synthesis activity. Thus, IF1 is not an essential protein for mice despite its ubiquitous presence in eukaryotes.
Highlights
Most of the ATP in aerobic cells is produced by ATP synthase in mitochondria coupled with proton flow driven by a proton motive force across membranes, which is generated by the respiratory chain
It is thought that when mitochondria lose proton motive force, the interior of the mitochondria become acidic and IF1 binds to ATP synthase to block wasteful ATP consumption [8]
A recent report showed that IF1 regulates haem synthesis in developing erythroblasts of zebra fish through the activity of ferrochelatase, which is sensitive to a pH alkaline shift in the mitochondria matrix space [19]
Summary
Most of the ATP in aerobic cells is produced by ATP synthase in mitochondria coupled with proton flow driven by a proton motive force across membranes, which is generated by the respiratory chain. IF1 is a small protein that can bind to ATP synthase and its soluble subcomplex F1-ATPase, and inhibit their ATP hydrolysis activities [1]. It is a nuclear-coded mitochondrial protein and is evolutionarily conserved from yeast to mammals [2,3]. Human cells with suppressed expression of IF1 have lower cellular ATP levels than control cells and produce higher levels of ROS (reactive oxygen species) [9,10].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call