ATPIF1 explained

ATPase inhibitor, mitochondrial is an enzyme that in humans is encoded by the ATPIF1 gene.^{[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.

It prevents ATPase from switching to ATP hydrolysis 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 antiparallel coiled 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]

Further reading

• Cabezón E, Runswick MJ, Leslie AG, Walker JE . The structure of bovine IF(1), the regulatory subunit of mitochondrial F-ATPase . EMBO J. . 20 . 24 . 6990–6996 . 2002 . 11742976 . 10.1093/emboj/20.24.6990 . 125800 .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–45 . 2004 . 14702039 . 10.1038/ng1285 . Suzuki Y . Nishikawa T . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Gerhard DS . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–2127 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Burwick NR . An Inhibitor of the F1 subunit of ATP synthase (IF1) modulates the activity of angiostatin on the endothelial cell surface . J. Biol. Chem. . 280 . 3 . 1740–1745 . 2005 . 15528193 . 10.1074/jbc.M405947200 . 1201548 . Wahl ML . Fang J . Zhong . Z . Moser . TL . Li . B . Capaldi . RA . Kenan . DJ . Pizzo . SV . free .
• Andersen JS . Nucleolar proteome dynamics . Nature . 433 . 7021 . 77–83 . 2005 . 15635413 . 10.1038/nature03207 . Lam YW . Leung AK . Ong . Shao-En . Lyon . Carol E. . Lamond . Angus I. . Mann . Matthias . 2005Natur.433...77A . 4344740 .
• Cortés-Hernández P . 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 . 2005 . 15809073 . 10.1016/j.bbrc.2005.03.064 . Domínguez-Ramírez L . Estrada-Bernal A . Montes-Sánchez . Delina G. . Zentella-Dehesa . Alejandro . De Gómez-Puyou . Marietta Tuena . Gómez-Puyou . Armando . García . José J. .
• Lim J . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–814 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . Hao T . Shaw C . Patel . Akash J. . Szabó . Gábor . Rual . Jean-François . Fisk . C. Joseph . Li . Ning . Smolyar . Alex . 13709685 . free .
• Ma J . Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects . Atherosclerosis . 191 . 1 . 63–72 . 2007 . 16806233 . 10.1016/j.atherosclerosis.2006.05.032 . Dempsey AA . Stamatiou D . Marshall . K . Liew . C .
• Contessi S . IF(1) distribution in HepG2 cells in relation to ecto-F(0)F (1)ATPsynthase and calmodulin . J. Bioenerg. Biomembr. . 39 . 4 . 291–300 . 2008 . 17851741 . 10.1007/s10863-007-9091-0 . Comelli M . Cmet S . Lippe . Giovanna . Mavelli . Irene . 85086145 .

Notes and References

1. Ichikawa N, Ushida S, Kawabata M, Masazumi Y . Nucleotide sequence of cDNA coding the mitochondrial precursor protein of the ATPase inhibitor from humans . Biosci Biotechnol Biochem . 63 . 12 . 2225–2227 . Mar 2000 . 10664857 . 10.1271/bbb.63.2225 . free .
2. Web site: Entrez Gene: ATPIF1 ATPase inhibitory factor 1.
3. Cabezon E, Butler PJ, Runswick MJ, Carbajo RJ, Walker JE . Homologous and heterologous inhibitory effects of ATPase inhibitor proteins on F-ATPases . J. Biol. Chem. . 277 . 44 . 41334–41 . November 2002 . 12186878 . 10.1074/jbc.M207169200 . 25160113 . free .
4. van Raaij MJ, Orriss GL, Montgomery MG, Runswick MJ, Fearnley IM, Skehel JM, Walker JE . The ATPase inhibitor protein from bovine heart mitochondria: the minimal inhibitory sequence . Biochemistry . 35 . 49 . 15618–25 . December 1996 . 8961923 . 10.1021/bi960628f .