AIFM1: Difference between revisions

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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Apoptosis-inducing factor 1, mitochondrial''' is a [[protein]] that in humans is encoded by the ''AIFM1'' [[gene]] on the X chromosome.<ref name="pmid9989411">{{cite journal | vauthors = 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 | title = Molecular characterization of mitochondrial apoptosis-inducing factor | journal = Nature | volume = 397 | issue = 6718 | pages = 441–6 | date = Feb 1999 | pmid = 9989411 | pmc =  | doi = 10.1038/17135 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: AIFM1 apoptosis-inducing factor, mitochondrion-associated, 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9131| accessdate = }}</ref> This protein localizes to the [[mitochondria]], as well as the [[Cell nucleus|nucleus]], where it carries out nuclear fragmentation as part of [[caspase]]-independent [[apoptosis]].<ref name=pmid24914854>{{cite journal | vauthors = Ferreira P, Villanueva R, Martínez-Júlvez M, Herguedas B, Marcuello C, Fernandez-Silva P, Cabon L, Hermoso JA, Lostao A, Susin SA, Medina M | title = Structural insights into the coenzyme mediated monomer-dimer transition of the pro-apoptotic apoptosis inducing factor | journal = Biochemistry | volume = 53 | issue = 25 | pages = 4204–15 | date = Jul 2014 | pmid = 24914854 | doi = 10.1021/bi500343r }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
| image = PBB_Protein_AIFM1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1gv4.
| PDB = {{PDB2|1gv4}}, {{PDB2|1m6i}}
| Name = Apoptosis-inducing factor, mitochondrion-associated, 1
| HGNCid = 8768
| Symbol = AIFM1
| AltSymbols =; AIF; MGC111425; PDCD8
| OMIM = 300169
| ECnumber = 
| Homologene = 3100
| MGIid = 1349419
| GeneAtlas_image1 = PBB_GE_AIFM1_205512_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0009055 |text = electron carrier activity}} {{GNF_GO|id=GO:0015036 |text = disulfide oxidoreductase activity}}
| Component = {{GNF_GO|id=GO:0005625 |text = soluble fraction}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}} {{GNF_GO|id=GO:0005792 |text = microsome}}
| Process = {{GNF_GO|id=GO:0006118 |text = electron transport}} {{GNF_GO|id=GO:0006309 |text = DNA fragmentation during apoptosis}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0008630 |text = DNA damage response, signal transduction resulting in induction of apoptosis}} {{GNF_GO|id=GO:0045454 |text = cell redox homeostasis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 9131
    | Hs_Ensembl = ENSG00000156709
    | Hs_RefseqProtein = NP_004199
    | Hs_RefseqmRNA = NM_004208
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 129091018
    | Hs_GenLoc_end = 129127489
    | Hs_Uniprot = O95831
    | Mm_EntrezGene = 26926
    | Mm_Ensembl = ENSMUSG00000036932
    | Mm_RefseqmRNA = NM_012019
    | Mm_RefseqProtein = NP_036149
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 44719571
    | Mm_GenLoc_end = 44758053
    | Mm_Uniprot = Q1L6K5
  }}
}}
'''Apoptosis-inducing factor, mitochondrion-associated, 1''', also known as '''AIFM1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: AIFM1 apoptosis-inducing factor, mitochondrion-associated, 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9131| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
AIFM1 is expressed as a 613-[[amino acid|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 [[flavin adenine dinucleotide|FAD]] [[cofactor (biochemistry)|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 [[Nicotinamide adenine dinucleotide|NAD]]-binding domains share the classical Rossmann topology with other flavoproteins and the NAD(P)H dependent reductase activity.<ref name=pmid24914854/>
{{PBB_Summary
| section_title =
| summary_text = 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 translocation of this protein to the nucleus where it effects chromosome condensation and fragmentation. In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Three alternative transcripts encoding different isoforms have been identified for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: AIFM1 apoptosis-inducing factor, mitochondrion-associated, 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9131| accessdate = }}</ref>
}}


==References==
Three [[alternative splicing|alternative]] transcripts encoding different [[isoform]]s have been identified for this gene.<ref name="entrez" /> Two alternatively spliced mRNA isoforms correspond to the inclusion/exclusion of the C-terminal and the reductase domains.<ref name=pmid24914854/> A pseudogene that is thought to be related to this gene has been identified on chromosome 10.<ref name="entrez" />
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Daugas E, Nochy D, Ravagnan L, ''et al.'' |title=Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. |journal=FEBS Lett. |volume=476 |issue= 3 |pages= 118-23 |year= 2000 |pmid= 10913597 |doi=  }}
*{{cite journal  | author=Ferri KF, Jacotot E, Blanco J, ''et al.'' |title=Mitochondrial control of cell death induced by HIV-1-encoded proteins. |journal=Ann. N. Y. Acad. Sci. |volume=926 |issue=  |pages= 149-64 |year= 2001 |pmid= 11193032 |doi=  }}
*{{cite journal  | author=Candé C, Cohen I, Daugas E, ''et al.'' |title=Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria. |journal=Biochimie |volume=84 |issue= 2-3 |pages= 215-22 |year= 2002 |pmid= 12022952 |doi=  }}
*{{cite journal  | author=Castedo M, Perfettini JL, Andreau K, ''et al.'' |title=Mitochondrial apoptosis induced by the HIV-1 envelope. |journal=Ann. N. Y. Acad. Sci. |volume=1010 |issue=  |pages= 19-28 |year= 2004 |pmid= 15033690 |doi=  }}
*{{cite journal  | author=Moon HS, Yang JS |title=Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells. |journal=Mol. Cells |volume=21 |issue= 1 |pages= 7-20 |year= 2006 |pmid= 16511342 |doi=  }}
*{{cite journal  | author=Glass L |title=Classification of biological networks by their qualitative dynamics. |journal=J. Theor. Biol. |volume=54 |issue= 1 |pages= 85-107 |year= 1976 |pmid= 1202295 |doi=  }}
*{{cite journal  | author=Andersson B, Wentland MA, Ricafrente JY, ''et al.'' |title=A "double adaptor" method for improved shotgun library construction. |journal=Anal. Biochem. |volume=236 |issue= 1 |pages= 107-13 |year= 1996 |pmid= 8619474 |doi= 10.1006/abio.1996.0138 }}
*{{cite journal  | author=Yu W, Andersson B, Worley KC, ''et al.'' |title=Large-scale concatenation cDNA sequencing. |journal=Genome Res. |volume=7 |issue= 4 |pages= 353-8 |year= 1997 |pmid= 9110174 |doi=  }}
*{{cite journal  | author=Susin SA, Zamzami N, Castedo M, ''et al.'' |title=The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis. |journal=J. Exp. Med. |volume=186 |issue= 1 |pages= 25-37 |year= 1997 |pmid= 9206994 |doi=  }}
*{{cite journal  | author=Susin SA, Lorenzo HK, Zamzami N, ''et al.'' |title=Mitochondrial release of caspase-2 and -9 during the apoptotic process. |journal=J. Exp. Med. |volume=189 |issue= 2 |pages= 381-94 |year= 1999 |pmid= 9892620 |doi=  }}
*{{cite journal  | author=Susin SA, Lorenzo HK, Zamzami N, ''et al.'' |title=Molecular characterization of mitochondrial apoptosis-inducing factor. |journal=Nature |volume=397 |issue= 6718 |pages= 441-6 |year= 1999 |pmid= 9989411 |doi= 10.1038/17135 }}
*{{cite journal  | author=Daugas E, Susin SA, Zamzami N, ''et al.'' |title=Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. |journal=FASEB J. |volume=14 |issue= 5 |pages= 729-39 |year= 2000 |pmid= 10744629 |doi=  }}
*{{cite journal  | author=Joza N, Susin SA, Daugas E, ''et al.'' |title=Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. |journal=Nature |volume=410 |issue= 6828 |pages= 549-54 |year= 2002 |pmid= 11279485 |doi= 10.1038/35069004 }}
*{{cite journal  | author=Ravagnan L, Gurbuxani S, Susin SA, ''et al.'' |title=Heat-shock protein 70 antagonizes apoptosis-inducing factor. |journal=Nat. Cell Biol. |volume=3 |issue= 9 |pages= 839-43 |year= 2001 |pmid= 11533664 |doi= 10.1038/ncb0901-839 }}
*{{cite journal  | author=Ye H, Cande C, Stephanou NC, ''et al.'' |title=DNA binding is required for the apoptogenic action of apoptosis inducing factor. |journal=Nat. Struct. Biol. |volume=9 |issue= 9 |pages= 680-4 |year= 2002 |pmid= 12198487 |doi= 10.1038/nsb836 }}
*{{cite journal  | author=Roumier T, Vieira HL, Castedo M, ''et al.'' |title=The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway. |journal=Cell Death Differ. |volume=9 |issue= 11 |pages= 1212-9 |year= 2003 |pmid= 12404120 |doi= 10.1038/sj.cdd.4401089 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
}}
{{refend}}


{{protein-stub}}
== Function ==
{{WikiDoc Sources}}
 
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 [[calpain]]s and/or [[cathepsin]]s into a soluble and proapoptogenic form that translocates to the nucleus, where it effects chromosome condensation and fragmentation.<ref name="entrez" /><ref name=pmid24914854/> In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9.<ref name="entrez" /> AIFM1 also contributes [[reductase]] activity in [[redox]] metabolism.<ref name=pmid24914854/>
 
== Clinical significance ==
Mutations in the AIFM1 [[gene]] are correlated with [[Charcot-Marie-Tooth disease|Charcot-Marie-Tooth disease (Cowchock syndrome)]].<ref name=pmid24914854/><ref name="pmid23217327">{{cite journal | vauthors = 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 | title = Cowchock syndrome is associated with a mutation in apoptosis-inducing factor | journal = Am. J. Hum. Genet. | volume = 91 | issue = 6 | pages = 1095–102 | year = 2012 | pmid = 23217327 | pmc = 3516602 | doi = 10.1016/j.ajhg.2012.10.008 }}</ref> At a cellular level, AIFM1 mutations result in deficiencies in [[oxidative phosphorylation]], leading to severe mitochondrial encephalomyopathy.<ref name="entrez" /> Clinical manifestations of this mutation are characterized by [[Muscle atrophy|muscular atrophy]], neuropathy, [[ataxia]], psychomotor regression, hearing loss and seizures.<ref name="pmid25583628">{{cite journal | vauthors = Kettwig M, Schubach M, Zimmermann FA, Klinge L, Mayr JA, Biskup S, Sperl W, Gärtner J, Huppke P | title = From ventriculomegaly to severe muscular atrophy: Expansion of the clinical spectrum related to mutations in AIFM1 | journal = Mitochondrion | volume = 21C | issue = | pages = 12–18 | year = 2015 | pmid = 25583628 | doi = 10.1016/j.mito.2015.01.001 }}</ref>
 
== Interactions ==
 
AIFM1 has been shown to [[Protein-protein interaction|interact]] with [[HSPA1A]].<ref name=pmid12930708>{{cite journal | vauthors = Ruchalski K, Mao H, Singh SK, Wang Y, Mosser DD, Li F, Schwartz JH, Borkan SC | title = HSP72 inhibits apoptosis-inducing factor release in ATP-depleted renal epithelial cells | journal = Am. J. Physiol., Cell Physiol. | volume = 285 | issue = 6 | pages = C1483–93 | date = Dec 2003 | pmid = 12930708 | doi = 10.1152/ajpcell.00049.2003 }}</ref><ref name=pmid11533664>{{cite journal | vauthors = Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, Mak T, Jäättelä M, Penninger JM, Garrido C, Kroemer G | title = Heat-shock protein 70 antagonizes apoptosis-inducing factor | journal = Nat. Cell Biol. | volume = 3 | issue = 9 | pages = 839–43 | date = Sep 2001 | pmid = 11533664 | doi = 10.1038/ncb0901-839 }}</ref>
 
== References ==
{{Reflist}}
{{Clear}}
 
== Further reading ==
{{Refbegin|35em}}
* {{cite journal | vauthors = Daugas E, Nochy D, Ravagnan L, Loeffler M, Susin SA, Zamzami N, Kroemer G | title = Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis | journal = FEBS Lett. | volume = 476 | issue = 3 | pages = 118–23 | year = 2000 | pmid = 10913597 | doi = 10.1016/S0014-5793(00)01731-2 }}
* {{cite journal | vauthors = Ferri KF, Jacotot E, Blanco J, Esté JA, Kroemer G | title = Mitochondrial control of cell death induced by HIV-1-encoded proteins | journal = Ann. N. Y. Acad. Sci. | volume = 926 | issue =  | pages = 149–64 | year = 2001 | pmid = 11193032 | doi = 10.1111/j.1749-6632.2000.tb05609.x }}
* {{cite journal | vauthors = Candé C, Cohen I, Daugas E, Ravagnan L, Larochette N, Zamzami N, Kroemer G | title = Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria | journal = Biochimie | volume = 84 | issue = 2–3 | pages = 215–22 | year = 2002 | pmid = 12022952 | doi = 10.1016/S0300-9084(02)01374-3 }}
* {{cite journal | vauthors = Castedo M, Perfettini JL, Andreau K, Roumier T, Piacentini M, Kroemer G | title = Mitochondrial apoptosis induced by the HIV-1 envelope | journal = Ann. N. Y. Acad. Sci. | volume = 1010 | issue =  | pages = 19–28 | year = 2004 | pmid = 15033690 | doi = 10.1196/annals.1299.004 }}
* {{cite journal | vauthors = Moon HS, Yang JS | title = Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells | journal = Mol. Cells | volume = 21 | issue = 1 | pages = 7–20 | year = 2006 | pmid = 16511342 | doi =  }}
* {{cite journal | vauthors = Glass L | title = Classification of biological networks by their qualitative dynamics | journal = J. Theor. Biol. | volume = 54 | issue = 1 | pages = 85–107 | year = 1976 | pmid = 1202295 | doi = 10.1016/S0022-5193(75)80056-7 }}
* {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Anal. Biochem. | volume = 236 | issue = 1 | pages = 107–13 | year = 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
* {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Res. | volume = 7 | issue = 4 | pages = 353–8 | year = 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
* {{cite journal | vauthors = Susin SA, Zamzami N, Castedo M, Daugas E, Wang HG, Geley S, Fassy F, Reed JC, Kroemer G | title = The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis | journal = J. Exp. Med. | volume = 186 | issue = 1 | pages = 25–37 | year = 1997 | pmid = 9206994 | pmc = 2198951 | doi = 10.1084/jem.186.1.25 }}
* {{cite journal | vauthors = Susin SA, Lorenzo HK, Zamzami N, Marzo I, Brenner C, Larochette N, Prévost MC, Alzari PM, Kroemer G | title = Mitochondrial release of caspase-2 and -9 during the apoptotic process | journal = J. Exp. Med. | volume = 189 | issue = 2 | pages = 381–94 | year = 1999 | pmid = 9892620 | pmc = 2192979 | doi = 10.1084/jem.189.2.381 }}
* {{cite journal | vauthors = Daugas E, Susin SA, Zamzami N, Ferri KF, Irinopoulou T, Larochette N, Prévost MC, Leber B, Andrews D, Penninger J, Kroemer G | title = Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis | journal = FASEB J. | volume = 14 | issue = 5 | pages = 729–39 | year = 2000 | pmid = 10744629 | doi =  }}
* {{cite journal | vauthors = 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 | title = Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death | journal = Nature | volume = 410 | issue = 6828 | pages = 549–54 | year = 2002 | pmid = 11279485 | doi = 10.1038/35069004 }}
* {{cite journal | vauthors = Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, Mak T, Jäättelä M, Penninger JM, Garrido C, Kroemer G | title = Heat-shock protein 70 antagonizes apoptosis-inducing factor | journal = Nat. Cell Biol. | volume = 3 | issue = 9 | pages = 839–43 | year = 2001 | pmid = 11533664 | doi = 10.1038/ncb0901-839 }}
* {{cite journal | vauthors = Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H | title = DNA binding is required for the apoptogenic action of apoptosis inducing factor | journal = Nat. Struct. Biol. | volume = 9 | issue = 9 | pages = 680–4 | year = 2002 | pmid = 12198487 | doi = 10.1038/nsb836 }}
* {{cite journal | vauthors = Roumier T, Vieira HL, Castedo M, Ferri KF, Boya P, Andreau K, Druillennec S, Joza N, Penninger JM, Roques B, Kroemer G | title = The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway | journal = Cell Death Differ. | volume = 9 | issue = 11 | pages = 1212–9 | year = 2003 | pmid = 12404120 | doi = 10.1038/sj.cdd.4401089 }}
{{Refend}}
 
== External links ==
* [http://AtlasGeneticsOncology.org/Genes/AIFM1ID44053chXq25.html AIFM1] on the [[Atlas of Genetics and Cytogenetics in Oncology and Haematology|Atlas of Genetics and Oncology]]
* {{UCSC gene info|AIFM1}}
 
{{PDB Gallery|geneid=9131}}
[[Category:Proteins]]

Revision as of 17:54, 29 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Apoptosis-inducing factor 1, mitochondrial is a protein that in humans is encoded by the AIFM1 gene on the X chromosome.[1][2] This protein localizes to the mitochondria, as well as the nucleus, where it carries out nuclear fragmentation as part of caspase-independent apoptosis.[3]

Structure

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 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.[3]

Three alternative transcripts encoding different isoforms have been identified for this gene.[2] Two alternatively spliced mRNA isoforms correspond to the inclusion/exclusion of the C-terminal and the reductase domains.[3] A pseudogene that is thought to be related to this gene has been identified on chromosome 10.[2]

Function

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 effects chromosome condensation and fragmentation.[2][3] In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9.[2] AIFM1 also contributes reductase activity in redox metabolism.[3]

Clinical significance

Mutations in the AIFM1 gene are correlated with Charcot-Marie-Tooth disease (Cowchock syndrome).[3][4] At a cellular level, AIFM1 mutations result in deficiencies in oxidative phosphorylation, leading to severe mitochondrial encephalomyopathy.[2] Clinical manifestations of this mutation are characterized by muscular atrophy, neuropathy, ataxia, psychomotor regression, hearing loss and seizures.[5]

Interactions

AIFM1 has been shown to interact with HSPA1A.[6][7]

References

  1. ↑ 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 (Feb 1999). "Molecular characterization of mitochondrial apoptosis-inducing factor". Nature. 397 (6718): 441–6. doi:10.1038/17135. PMID 9989411.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "Entrez Gene: AIFM1 apoptosis-inducing factor, mitochondrion-associated, 1".
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Ferreira P, Villanueva R, Martínez-Júlvez M, Herguedas B, Marcuello C, Fernandez-Silva P, Cabon L, Hermoso JA, Lostao A, Susin SA, Medina M (Jul 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.
  4. ↑ 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 (2012). "Cowchock syndrome is associated with a mutation in apoptosis-inducing factor". Am. J. Hum. Genet. 91 (6): 1095–102. doi:10.1016/j.ajhg.2012.10.008. PMC 3516602. PMID 23217327.
  5. ↑ Kettwig M, Schubach M, Zimmermann FA, Klinge L, Mayr JA, Biskup S, Sperl W, Gärtner J, Huppke P (2015). "From ventriculomegaly to severe muscular atrophy: Expansion of the clinical spectrum related to mutations in AIFM1". Mitochondrion. 21C: 12–18. doi:10.1016/j.mito.2015.01.001. PMID 25583628.
  6. ↑ Ruchalski K, Mao H, Singh SK, Wang Y, Mosser DD, Li F, Schwartz JH, Borkan SC (Dec 2003). "HSP72 inhibits apoptosis-inducing factor release in ATP-depleted renal epithelial cells". Am. J. Physiol., Cell Physiol. 285 (6): C1483–93. doi:10.1152/ajpcell.00049.2003. PMID 12930708.
  7. ↑ Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, Mak T, Jäättelä M, Penninger JM, Garrido C, Kroemer G (Sep 2001). "Heat-shock protein 70 antagonizes apoptosis-inducing factor". Nat. Cell Biol. 3 (9): 839–43. doi:10.1038/ncb0901-839. PMID 11533664.

Further reading

External links

Retrieved from "https://www.wikidoc.org/index.php?title=AIFM1&oldid=1423394"