AIFM2: Difference between revisions

'''Apoptosis-inducing factor 2''' (AIFM2), also known as ferroptosis suppressor protein 1 (FSP1), apoptosis-inducing factor-homologous mitochondrion-associated inducer of death (AMID), is a [[protein]] that in humans is encoded by the ''AIFM2'' [[gene]], also known as p53-responsive gene 3 (PRG3), on chromosome 10.<ref name="pmid12135761">{{cite journal | vauthors = Ohiro Y, Garkavtsev I, Kobayashi S, Sreekumar KR, Nantz R, Higashikubo BT, Duffy SL, Higashikubo R, Usheva A, Gius D, Kley N, Horikoshi N | title = A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF) | journal = FEBS Letters | volume = 524 | issue = 1–3 | pages = 163–71 | date = July 2002 | pmid = 12135761 | doi = 10.1016/S0014-5793(02)03049-1 | s2cid = 6972218 | doi-access = free }}</ref><ref name="pmid11980907">{{cite journal | vauthors = Wu M, Xu LG, Li X, Zhai Z, Shu HB | title = AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis | journal = The Journal of Biological Chemistry | volume = 277 | issue = 28 | pages = 25617–23 | date = July 2002 | pmid = 11980907 | doi = 10.1074/jbc.M202285200 | doi-access = free }}</ref><ref name="pmid15958387">{{cite journal | vauthors = Marshall KR, Gong M, Wodke L, Lamb JH, Jones DJ, Farmer PB, Scrutton NS, Munro AW | title = The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity | journal = The Journal of Biological Chemistry | volume = 280 | issue = 35 | pages = 30735–40 | date = September 2005 | pmid = 15958387 | doi = 10.1074/jbc.M414018200 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: AIFM2 apoptosis-inducing factor, mitochondrion-associated, 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84883}}</ref><ref name=":0Doll_2019">{{Citecite journal |last vauthors = Doll |first=SebastianS, |last2=Freitas |first2=FlorencioFP, Porto |last3=Shah |first3=RonR, |last4=Aldrovandi |first4=MacelerM, |last5=da Silva |first5=MileneMC, Costa |last6=Ingold |first6=IrinaI, |last7=Goya Grocin |first7=AndreaA, |last8=Xavier da Silva |first8=ThamaraTN, Nishida |last9=Panzilius |first9=ElenaE, |last10=Scheel |first10=ChristinaCH, H. |last11=Mourão |first11=AndréA, |last12=Buday |first12=KatalinK, |last13=Sato |first13=MamiM, |last14=Wanninger |first14=JonasJ, |last15=Vignane |first15=ThibautT, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O'Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli JP, Conrad M |date=2019 display-11authors = 6 | title = FSP1 is a glutathione-independent ferroptosis suppressor |url=https://www.nature.com/articles/s41586-019-1707-0 |journal = Nature |language=en |volume = 575 | issue = 7784 | pages = 693–698 | date = November 2019 | pmid = 31634899 | doi = 10.1038/s41586-019-1707-0 |issn=1476-4687}}</ref><ref name=":1Bersuker_2019">{{Citecite journal |last vauthors = Bersuker |first=KirillK, |last2=Hendricks |first2=JosephJM, M. |last3=Li |first3=ZhipengZ, |last4=Magtanong |first4=LeslieL, |last5=Ford |first5=BreannaB, |last6=Tang |first6=PeterPH, H. |last7=Roberts |first7=MelissaMA, A. |last8=Tong |first8=BingqiB, |last9=Maimone |first9=ThomasTJ, J. |last10=Zoncu |first10=RobertoR, |last11=Bassik |first11=MichaelMC, C. |last12=Nomura |first12=DanielDK, K. |last13=Dixon |first13=ScottSJ, J.Olzmann JA |last14=Olzmann |first14display-authors =James A.6 |date=2019-11 |title = The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis |url=https://www.nature.com/articles/s41586-019-1705-2 |journal = Nature |language=en |volume = 575 | issue = 7784 | pages = 688–692 | date = November 2019 | pmid = 31634900 | pmc = 6883167 | doi = 10.1038/s41586-019-1705-2 |issn=1476-4687 |pmc=PMC6883167 |pmid=31634900}}</ref>

The AIFM2 gene encodes the FSP1 protein encoded by this gene has significant [[Homology (biology)|homology]] to [[NADH]] [[oxidoreductase]]s and the [[apoptosis-inducing factor]] PDCD8/[[Apoptosis-inducing factor|AIF]]. Although it was originally proposed that this protein induce [[apoptosis]] due to its similarity with AIF, findings from James Olzmann's group at UC Berkeley <ref name=":1Bersuker_2019" /> and Marcus Conrad's group at the Helmholtz Institute <ref name=":0Doll_2019" /> demonstrated that the primary cellular function of FSP1 is to suppress lipid peroxidation and the induction of the regulated, non-apoptotic cell death pathway known as [[ferroptosis]]. Mechanistically, FSP1 reduces oxidized coenzyme Q10 (i.e., ubiquinone) to its reduced form (i.e., ubiquinol), which functions as an excellent lipophilic antioxidant to prevent the propagation of lipid peroxidation.<ref name=":0Doll_2019" /><ref name=":1Bersuker_2019" /> FSP1 also may act through the reduction of other molecules, such as vitamin E and vitamin K.