The inhibitor protein IF₁ from mammalian mitochondria inhibits ATP hydrolysis but not ATP synthesis by the ATP synthase complex.

ABSTRACT: The hydrolytic activity of the ATP synthase in bovine mitochondria is inhibited by a protein called IF₁, but bovine IF₁ has no effect on the synthetic activity of the bovine enzyme in mitochondrial vesicles in the presence of a proton motive force. In contrast, it has been suggested based on indirect observations that human IF_I inhibits both the hydrolytic and synthetic activities of the human ATP synthase and that the activity of human IF₁ is regulated by the phosphorylation of Ser-14 of mature IF₁. Here, we have made both human and bovine IF₁ which are 81 and 84 amino acids long, respectively, and identical in 71.4% of their amino acids and have investigated their inhibitory effects on the hydrolytic and synthetic activities of ATP synthase in bovine submitochondrial particles. Over a wide range of conditions, including physiological conditions, both human and bovine IF₁ are potent inhibitors of ATP hydrolysis, with no effect on ATP synthesis. Also, substitution of Ser-14 with phosphomimetic aspartic and glutamic acids had no effect on inhibitory properties, and Ser-14 is not conserved throughout mammals. Therefore, it is unlikely that the inhibitory activity of mammalian IF₁ is regulated by phosphorylation of this residue.

SUBMITTER: Carroll J 

PROVIDER: S-EPMC10906535 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature