ATPase inhibitor, mitochondrial is an enzyme that in humans is encoded by the ATPIF1gene.[1][2]
This gene encodes a mitochondrial ATPase inhibitor. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified.[2]
It prevents ATPase from switching to ATPhydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation [3] ATP synthase inhibitor forms a one-to-one complex with the F1 ATPase, possibly by binding at the alpha-beta interface. It is thought to inhibit ATP synthesis by preventing the release of ATP.[4] The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH, the inhibitor forms a dimer via antiparallelcoiled coil interactions between the C-terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity.[3]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty three tests were carried out on mutant mice and three significant abnormalities were observed.[9]Homozygous mutant animals displayed hyperactivity and brain dysmorphology, while males also had decreased circulating alkaline phosphatase levels.[9]
↑Ichikawa N, Ushida S, Kawabata M, Masazumi Y (Mar 2000). "Nucleotide sequence of cDNA coding the mitochondrial precursor protein of the ATPase inhibitor from humans". Biosci Biotechnol Biochem. 63 (12): 2225–2227. doi:10.1271/bbb.63.2225. PMID10664857.
↑ 9.09.19.29.3Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. doi:10.1038/ng1285. PMID14702039.
Cortés-Hernández P, Domínguez-Ramírez L, Estrada-Bernal A, et al. (2005). "The inhibitor protein of the F1F0-ATP synthase is associated to the external surface of endothelial cells". Biochem. Biophys. Res. Commun. 330 (3): 844–849. doi:10.1016/j.bbrc.2005.03.064. PMID15809073.
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–814. doi:10.1016/j.cell.2006.03.032. PMID16713569.
Ma J, Dempsey AA, Stamatiou D, et al. (2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis. 191 (1): 63–72. doi:10.1016/j.atherosclerosis.2006.05.032. PMID16806233.
Contessi S, Comelli M, Cmet S, et al. (2008). "IF(1) distribution in HepG2 cells in relation to ecto-F(0)F (1)ATPsynthase and calmodulin". J. Bioenerg. Biomembr. 39 (4): 291–300. doi:10.1007/s10863-007-9091-0. PMID17851741.
