Mitochondrial F₁F_OATP synthase determines the local proton motive force in cristae tips

Abstract

The classical view of oxidative phosphorylation is that a proton motive force PMF generated by the respiratory chain complexes fuels ATP synthesis. Under glycolytic conditions, ATP synthase in its reverse mode also can contribute to the PMF. Here, we dissected the two functions of ATP synthase and the role of the inhibitory factor 1 (IF1) under different metabolic conditions in detail. pH profiles of mitochondrial sub-compartments were recorded with high spatial resolution in live mammalian cells by positioning a pH-sensor directly at F1 and FO of ATP synthase, complex IV and in the matrix. Our results clearly show that ATP synthase activity is substantially controlling the PMF and that IF1 is essential under OXPHOS conditions to prevent reverse ATP synthase activity due to an almost negligible delta pH.

IF1 Protein Controls Aging Rate

“…A recent paper has further confirmed one of the assertions of this present paper, and its patent application predecessors (e.g. [405–406]), that (to quote it) “IF1 is required to prevent the onset of ATP hydrolysis under OXPHOS conditions”, “IF1 is essential under OXPHOS conditions to prevent reverse ATP synthase activity”, “our data clearly show that IF1 is necessary to block ATP hydrolysis under OXPHOS conditions”, “to prevent futile ATP synthesis/hydrolysis cycles by reverse ATP synthase activity and ATP hydrolysis, IF1 is essential even and especially under OXPHOS conditions”, “IF1 is beneficial for ATP production even under OXPHOS conditions”, “ATP levels were lower in IF1-KO cells under OXPHOS conditions”, “clearly, this data demonstrates the importance of IF1 to block futile ATP hydrolysis under OXPHOS conditions” [407].…”