Apoptosis-inducing factor 1, mitochondrial is a protein that in humans is encoded by the AIFM1gene on the X chromosome.[5][6] This protein localizes to the mitochondria, as well as the nucleus, where it carries out nuclear fragmentation as part of caspase-independent apoptosis.[7]
AIFM1 is expressed as a 613-residue precursor protein that containing a mitochondrial targeting sequence (MTS) at its N-terminal and two nuclear leading sequences (NLS). Once imported into the mitochondria, the first 54 residues of the N-terminal are cleaved to produce the mature protein, which inserts into the inner mitochondrial membrane. The mature protein incorporates the FADcofactor and folds into three structural domains: the FAD-binding domain, the NAD-binding domain, and the C-terminal. While the C-terminal is responsible for the proapoptotic activity of AIFM1, the FAD-binding and NAD-binding domains share the classical Rossmann topology with other flavoproteins and the NAD(P)H dependent reductase activity.[7]
Three alternative transcripts encoding different isoforms have been identified for this gene.[6] Two alternatively spliced mRNA isoforms correspond to the inclusion/exclusion of the C-terminal and the reductase domains.[7] A pseudogene that is thought to be related to this gene has been identified on chromosome 10.[6]
Functionedit
This gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells that is found in the mitochondrial intermembrane space in healthy cells. Induction of apoptosis results in the cleavage of this protein at residue 102 by calpains and/or cathepsins into a soluble and proapoptogenic form that translocates to the nucleus, where it affects chromosome condensation and fragmentation.[6][7] In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9.[6] AIFM1 also contributes reductase activity in redox metabolism.[7]
Phylogenetic analysis indicates that the divergence of the AIFM1 and other human AIFs (AIFM2a and AIFM3) sequences occurred before the divergence of eukaryotes. This conclusion is supported by domain architecture of these proteins. Both eukaryotic and eubacterial AIFM1 proteins contain additional domain AIF_C.[12]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000156709 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000036932 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G (February 1999). "Molecular characterization of mitochondrial apoptosis-inducing factor". Nature. 397 (6718): 441–6. Bibcode:1999Natur.397..441S. doi:10.1038/17135. PMID 9989411. S2CID 204991081.
^ abcdefFerreira P, Villanueva R, Martínez-Júlvez M, Herguedas B, Marcuello C, Fernandez-Silva P, Cabon L, Hermoso JA, Lostao A, Susin SA, Medina M (July 2014). "Structural insights into the coenzyme mediated monomer-dimer transition of the pro-apoptotic apoptosis inducing factor". Biochemistry. 53 (25): 4204–15. doi:10.1021/bi500343r. PMID 24914854.
^Rinaldi C, Grunseich C, Sevrioukova IF, Schindler A, Horkayne-Szakaly I, Lamperti C, Landouré G, Kennerson ML, Burnett BG, Bönnemann C, Biesecker LG, Ghezzi D, Zeviani M, Fischbeck KH (December 2012). "Cowchock syndrome is associated with a mutation in apoptosis-inducing factor". American Journal of Human Genetics. 91 (6): 1095–102. doi:10.1016/j.ajhg.2012.10.008. PMC3516602. PMID 23217327.
^Kettwig M, Schubach M, Zimmermann FA, Klinge L, Mayr JA, Biskup S, Sperl W, Gärtner J, Huppke P (March 2015). "From ventriculomegaly to severe muscular atrophy: expansion of the clinical spectrum related to mutations in AIFM1". Mitochondrion. 21: 12–8. doi:10.1016/j.mito.2015.01.001. PMID 25583628.
^Ruchalski K, Mao H, Singh SK, Wang Y, Mosser DD, Li F, Schwartz JH, Borkan SC (December 2003). "HSP72 inhibits apoptosis-inducing factor release in ATP-depleted renal epithelial cells". American Journal of Physiology. Cell Physiology. 285 (6): C1483–93. doi:10.1152/ajpcell.00049.2003. PMID 12930708.
^Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, Mak T, Jäättelä M, Penninger JM, Garrido C, Kroemer G (September 2001). "Heat-shock protein 70 antagonizes apoptosis-inducing factor". Nature Cell Biology. 3 (9): 839–43. doi:10.1038/ncb0901-839. PMID 11533664. S2CID 21164493.
^Klim J, Gładki A, Kucharczyk R, Zielenkiewicz U, Kaczanowski S (May 2018). "Ancestral State Reconstruction of the Apoptosis Machinery in the Common Ancestor of Eukaryotes". G3. 8 (6): 2121–2134. doi:10.1534/g3.118.200295. PMC5982838. PMID 29703784.
Further readingedit
Daugas E, Nochy D, Ravagnan L, Loeffler M, Susin SA, Zamzami N, Kroemer G (July 2000). "Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis". FEBS Letters. 476 (3): 118–23. doi:10.1016/S0014-5793(00)01731-2. PMID 10913597. S2CID 2156881.
Ferri KF, Jacotot E, Blanco J, Esté JA, Kroemer G (2001). "Mitochondrial control of cell death induced by HIV-1-encoded proteins". Annals of the New York Academy of Sciences. 926: 149–64. doi:10.1111/j.1749-6632.2000.tb05609.x. PMID 11193032. S2CID 21997163.
Candé C, Cohen I, Daugas E, Ravagnan L, Larochette N, Zamzami N, Kroemer G (2002). "Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria". Biochimie. 84 (2–3): 215–22. doi:10.1016/S0300-9084(02)01374-3. PMID 12022952.
Castedo M, Perfettini JL, Andreau K, Roumier T, Piacentini M, Kroemer G (December 2003). "Mitochondrial apoptosis induced by the HIV-1 envelope". Annals of the New York Academy of Sciences. 1010 (1): 19–28. Bibcode:2003NYASA1010...19C. doi:10.1196/annals.1299.004. PMID 15033690. S2CID 37073602.
Moon HS, Yang JS (February 2006). "Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells". Molecules and Cells. 21 (1): 7–20. doi:10.1016/s1016-8478(23)12897-4. PMID 16511342.
Glass L (October 1975). "Classification of biological networks by their qualitative dynamics". Journal of Theoretical Biology. 54 (1): 85–107. Bibcode:1975JThBi..54...85G. doi:10.1016/S0022-5193(75)80056-7. PMID 1202295.
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC139146. PMID 9110174.
Susin SA, Zamzami N, Castedo M, Daugas E, Wang HG, Geley S, Fassy F, Reed JC, Kroemer G (July 1997). "The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis". The Journal of Experimental Medicine. 186 (1): 25–37. doi:10.1084/jem.186.1.25. PMC2198951. PMID 9206994.
Susin SA, Lorenzo HK, Zamzami N, Marzo I, Brenner C, Larochette N, Prévost MC, Alzari PM, Kroemer G (January 1999). "Mitochondrial release of caspase-2 and -9 during the apoptotic process". The Journal of Experimental Medicine. 189 (2): 381–94. doi:10.1084/jem.189.2.381. PMC2192979. PMID 9892620.
Daugas E, Susin SA, Zamzami N, Ferri KF, Irinopoulou T, Larochette N, Prévost MC, Leber B, Andrews D, Penninger J, Kroemer G (April 2000). "Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis". FASEB Journal. 14 (5): 729–39. doi:10.1096/fasebj.14.5.729. PMID 10744629. S2CID 7289409.
Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, Sasaki T, Elia AJ, Cheng HY, Ravagnan L, Ferri KF, Zamzami N, Wakeham A, Hakem R, Yoshida H, Kong YY, Mak TW, Zúñiga-Pflücker JC, Kroemer G, Penninger JM (March 2001). "Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death". Nature. 410 (6828): 549–54. Bibcode:2001Natur.410..549J. doi:10.1038/35069004. PMID 11279485. S2CID 4387964.
Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, Mak T, Jäättelä M, Penninger JM, Garrido C, Kroemer G (September 2001). "Heat-shock protein 70 antagonizes apoptosis-inducing factor". Nature Cell Biology. 3 (9): 839–43. doi:10.1038/ncb0901-839. PMID 11533664. S2CID 21164493.
Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H (September 2002). "DNA binding is required for the apoptogenic action of apoptosis inducing factor". Nature Structural Biology. 9 (9): 680–4. doi:10.1038/nsb836. PMID 12198487. S2CID 7819466.
Roumier T, Vieira HL, Castedo M, Ferri KF, Boya P, Andreau K, Druillennec S, Joza N, Penninger JM, Roques B, Kroemer G (November 2002). "The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway". Cell Death and Differentiation. 9 (11): 1212–9. doi:10.1038/sj.cdd.4401089. PMID 12404120.
Human AIFM1 genome location and AIFM1 gene details page in the UCSC Genome Browser.
April 11, 2024
aifm1, apoptosis, inducing, factor, mitochondrial, protein, that, humans, encoded, gene, chromosome, this, protein, localizes, mitochondria, well, nucleus, where, carries, nuclear, fragmentation, part, caspase, independent, apoptosis, available, structurespdbo. Apoptosis inducing factor 1 mitochondrial is a protein that in humans is encoded by the AIFM1 gene on the X chromosome 5 6 This protein localizes to the mitochondria as well as the nucleus where it carries out nuclear fragmentation as part of caspase independent apoptosis 7 AIFM1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1M6I 4BUR 4BV6 4FDC 4LII 5FS7 5FS9 5FS6 5FS8IdentifiersAliasesAIFM1 AIF CMT2D CMTX4 COWCK COXPD6 NADMR NAMSD PDCD8 DFNX5 apoptosis inducing factor mitochondria associated 1 apoptosis inducing factor mitochondria associated 1 AUNX1 SEMDHLExternal IDsOMIM 300169 MGI 1349419 HomoloGene 3100 GeneCards AIFM1Gene location Human Chr X chromosome human 1 BandXq26 1Start130 124 666 bp 1 End130 165 879 bp 1 Gene location Mouse Chr X chromosome mouse 2 BandX A5 X 25 68 cMStart47 563 821 bp 2 End47 602 440 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inkidneyleft ventricleright lobe of liverleft adrenal glandgastrocnemius musclerectumright ventricleright uterine tubeduodenumbody of stomachTop expressed ininterventricular septumchoroid plexuskidneyproximal tubulesoleus musclebrown adipose tissuecondyleplantaris muscleadrenal glandextraocular muscleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein binding protein dimerization activity oxidoreductase activity flavin adenine dinucleotide binding NAD P H oxidase H2O2 forming activity FAD binding oxidoreductase activity acting on NAD P H DNA bindingCellular componentmitochondrial inner membrane cytoplasm cytosol membrane perinuclear region of cytoplasm mitochondrial intermembrane space mitochondrion nucleusBiological processneuron apoptotic process response to ischemia chromosome condensation cellular response to oxygen glucose deprivation activation of cysteine type endopeptidase activity involved in apoptotic process positive regulation of neuron apoptotic process regulation of apoptotic DNA fragmentation cellular response to hydrogen peroxide intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress positive regulation of apoptotic process cellular response to nitric oxide response to L glutamate positive regulation of cell death mitochondrial respiratory chain complex I assembly response to toxic substance cellular response to estradiol stimulus neuron differentiation cellular response to aldosterone apoptotic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez913126926EnsemblENSG00000156709ENSMUSG00000036932UniProtO95831Q9Z0X1RefSeq mRNA NM 001130846NM 001130847NM 004208NM 145812NM 145813NM 001290364NM 012019RefSeq protein NP 001124318NP 001124319NP 004199NP 665811NP 001277293NP 036149Location UCSC Chr X 130 12 130 17 MbChr X 47 56 47 6 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure 2 Function 3 Clinical significance 4 Interactions 5 Evolution 6 References 7 Further reading 8 External linksStructure editAIFM1 is expressed as a 613 residue precursor protein that containing a mitochondrial targeting sequence MTS at its N terminal and two nuclear leading sequences NLS Once imported into the mitochondria the first 54 residues of the N terminal are cleaved to produce the mature protein which inserts into the inner mitochondrial membrane The mature protein incorporates the FAD cofactor and folds into three structural domains the FAD binding domain the NAD binding domain and the C terminal While the C terminal is responsible for the proapoptotic activity of AIFM1 the FAD binding and NAD binding domains share the classical Rossmann topology with other flavoproteins and the NAD P H dependent reductase activity 7 Three alternative transcripts encoding different isoforms have been identified for this gene 6 Two alternatively spliced mRNA isoforms correspond to the inclusion exclusion of the C terminal and the reductase domains 7 A pseudogene that is thought to be related to this gene has been identified on chromosome 10 6 Function editThis gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells that is found in the mitochondrial intermembrane space in healthy cells Induction of apoptosis results in the cleavage of this protein at residue 102 by calpains and or cathepsins into a soluble and proapoptogenic form that translocates to the nucleus where it affects chromosome condensation and fragmentation 6 7 In addition this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase 9 6 AIFM1 also contributes reductase activity in redox metabolism 7 Clinical significance editMutations in the AIFM1 gene are correlated with Charcot Marie Tooth disease Cowchock syndrome 7 8 At a cellular level AIFM1 mutations result in deficiencies in oxidative phosphorylation leading to severe mitochondrial encephalomyopathy 6 Clinical manifestations of this mutation are characterized by muscular atrophy neuropathy ataxia psychomotor regression hearing loss and seizures 9 Interactions editAIFM1 has been shown to interact with HSPA1A 10 11 Evolution editPhylogenetic analysis indicates that the divergence of the AIFM1 and other human AIFs AIFM2a and AIFM3 sequences occurred before the divergence of eukaryotes This conclusion is supported by domain architecture of these proteins Both eukaryotic and eubacterial AIFM1 proteins contain additional domain AIF C 12 References edit a b c GRCh38 Ensembl release 89 ENSG00000156709 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000036932 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Susin SA Lorenzo HK Zamzami N Marzo I Snow BE Brothers GM Mangion J Jacotot E Costantini P Loeffler M Larochette N Goodlett DR Aebersold R Siderovski DP Penninger JM Kroemer G February 1999 Molecular characterization of mitochondrial apoptosis inducing factor Nature 397 6718 441 6 Bibcode 1999Natur 397 441S doi 10 1038 17135 PMID 9989411 S2CID 204991081 a b c d e f Entrez Gene AIFM1 apoptosis inducing factor mitochondrion associated 1 a b c d e f Ferreira P Villanueva R Martinez Julvez M Herguedas B Marcuello C Fernandez Silva P Cabon L Hermoso JA Lostao A Susin SA Medina M July 2014 Structural insights into the coenzyme mediated monomer dimer transition of the pro apoptotic apoptosis inducing factor Biochemistry 53 25 4204 15 doi 10 1021 bi500343r PMID 24914854 Rinaldi C Grunseich C Sevrioukova IF Schindler A Horkayne Szakaly I Lamperti C Landoure G Kennerson ML Burnett BG Bonnemann C Biesecker LG Ghezzi D Zeviani M Fischbeck KH December 2012 Cowchock syndrome is associated with a mutation in apoptosis inducing factor American Journal of Human Genetics 91 6 1095 102 doi 10 1016 j ajhg 2012 10 008 PMC 3516602 PMID 23217327 Kettwig M Schubach M Zimmermann FA Klinge L Mayr JA Biskup S Sperl W Gartner J Huppke P March 2015 From ventriculomegaly to severe muscular atrophy expansion of the clinical spectrum related to mutations in AIFM1 Mitochondrion 21 12 8 doi 10 1016 j mito 2015 01 001 PMID 25583628 Ruchalski K Mao H Singh SK Wang Y Mosser DD Li F Schwartz JH Borkan SC December 2003 HSP72 inhibits apoptosis inducing factor release in ATP depleted renal epithelial cells American Journal of Physiology Cell Physiology 285 6 C1483 93 doi 10 1152 ajpcell 00049 2003 PMID 12930708 Ravagnan L Gurbuxani S Susin SA Maisse C Daugas E Zamzami N Mak T Jaattela M Penninger JM Garrido C Kroemer G September 2001 Heat shock protein 70 antagonizes apoptosis inducing factor Nature Cell Biology 3 9 839 43 doi 10 1038 ncb0901 839 PMID 11533664 S2CID 21164493 Klim J Gladki A Kucharczyk R Zielenkiewicz U Kaczanowski S May 2018 Ancestral State Reconstruction of the Apoptosis Machinery in the Common Ancestor of Eukaryotes G3 8 6 2121 2134 doi 10 1534 g3 118 200295 PMC 5982838 PMID 29703784 Further reading editDaugas E Nochy D Ravagnan L Loeffler M Susin SA Zamzami N Kroemer G July 2000 Apoptosis inducing factor AIF a ubiquitous mitochondrial oxidoreductase involved in apoptosis FEBS Letters 476 3 118 23 doi 10 1016 S0014 5793 00 01731 2 PMID 10913597 S2CID 2156881 Ferri KF Jacotot E Blanco J Este JA Kroemer G 2001 Mitochondrial control of cell death induced by HIV 1 encoded proteins Annals of the New York Academy of Sciences 926 149 64 doi 10 1111 j 1749 6632 2000 tb05609 x PMID 11193032 S2CID 21997163 Cande C Cohen I Daugas E Ravagnan L Larochette N Zamzami N Kroemer G 2002 Apoptosis inducing factor AIF a novel caspase independent death effector released from mitochondria Biochimie 84 2 3 215 22 doi 10 1016 S0300 9084 02 01374 3 PMID 12022952 Castedo M Perfettini JL Andreau K Roumier T Piacentini M Kroemer G December 2003 Mitochondrial apoptosis induced by the HIV 1 envelope Annals of the New York Academy of Sciences 1010 1 19 28 Bibcode 2003NYASA1010 19C doi 10 1196 annals 1299 004 PMID 15033690 S2CID 37073602 Moon HS Yang JS February 2006 Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells Molecules and Cells 21 1 7 20 doi 10 1016 s1016 8478 23 12897 4 PMID 16511342 Glass L October 1975 Classification of biological networks by their qualitative dynamics Journal of Theoretical Biology 54 1 85 107 Bibcode 1975JThBi 54 85G doi 10 1016 S0022 5193 75 80056 7 PMID 1202295 Andersson B Wentland MA Ricafrente JY Liu W Gibbs RA April 1996 A double adaptor method for improved shotgun library construction Analytical Biochemistry 236 1 107 13 doi 10 1006 abio 1996 0138 PMID 8619474 Yu W Andersson B Worley KC Muzny DM Ding Y Liu W Ricafrente JY Wentland MA Lennon G Gibbs RA April 1997 Large scale concatenation cDNA sequencing Genome Research 7 4 353 8 doi 10 1101 gr 7 4 353 PMC 139146 PMID 9110174 Susin SA Zamzami N Castedo M Daugas E Wang HG Geley S Fassy F Reed JC Kroemer G July 1997 The central executioner of apoptosis multiple connections between protease activation and mitochondria in Fas APO 1 CD95 and ceramide induced apoptosis The Journal of Experimental Medicine 186 1 25 37 doi 10 1084 jem 186 1 25 PMC 2198951 PMID 9206994 Susin SA Lorenzo HK Zamzami N Marzo I Brenner C Larochette N Prevost MC Alzari PM Kroemer G January 1999 Mitochondrial release of caspase 2 and 9 during the apoptotic process The Journal of Experimental Medicine 189 2 381 94 doi 10 1084 jem 189 2 381 PMC 2192979 PMID 9892620 Daugas E Susin SA Zamzami N Ferri KF Irinopoulou T Larochette N Prevost MC Leber B Andrews D Penninger J Kroemer G April 2000 Mitochondrio nuclear translocation of AIF in apoptosis and necrosis FASEB Journal 14 5 729 39 doi 10 1096 fasebj 14 5 729 PMID 10744629 S2CID 7289409 Joza N Susin SA Daugas E Stanford WL Cho SK Li CY Sasaki T Elia AJ Cheng HY Ravagnan L Ferri KF Zamzami N Wakeham A Hakem R Yoshida H Kong YY Mak TW Zuniga Pflucker JC Kroemer G Penninger JM March 2001 Essential role of the mitochondrial apoptosis inducing factor in programmed cell death Nature 410 6828 549 54 Bibcode 2001Natur 410 549J doi 10 1038 35069004 PMID 11279485 S2CID 4387964 Ravagnan L Gurbuxani S Susin SA Maisse C Daugas E Zamzami N Mak T Jaattela M Penninger JM Garrido C Kroemer G September 2001 Heat shock protein 70 antagonizes apoptosis inducing factor Nature Cell Biology 3 9 839 43 doi 10 1038 ncb0901 839 PMID 11533664 S2CID 21164493 Ye H Cande C Stephanou NC Jiang S Gurbuxani S Larochette N Daugas E Garrido C Kroemer G Wu H September 2002 DNA binding is required for the apoptogenic action of apoptosis inducing factor Nature Structural Biology 9 9 680 4 doi 10 1038 nsb836 PMID 12198487 S2CID 7819466 Roumier T Vieira HL Castedo M Ferri KF Boya P Andreau K Druillennec S Joza N Penninger JM Roques B Kroemer G November 2002 The C terminal moiety of HIV 1 Vpr induces cell death via a caspase independent mitochondrial pathway Cell Death and Differentiation 9 11 1212 9 doi 10 1038 sj cdd 4401089 PMID 12404120 External links editAIFM1 on the Atlas of Genetics and Oncology Human AIFM1 genome location and AIFM1 gene details page in the UCSC Genome Browser Retrieved from https en wikipedia org w index php title AIFM1 amp oldid 1206436653, wikipedia, wiki, book, books, library,
