Apoptosis-inducing factor 1, mitochondrial

Definition:

Functions both as NADH oxidoreductase and as regulator of apoptosis. In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (By similarity). The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA. Binds to DNA in a sequence-independent manner. Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. In contrast, participates in normal mitochondrial metabolism. Plays an important role in the regulation of respiratory chain biogenesis by interacting with CHCHD4 and controlling CHCHD4 mitochondrial import.; [Isoform 4]: Has NADH oxidoreductase activity. Does not induce nuclear apoptosis.; [Isoform 5]: Pro-apoptotic isoform.

References:

[1]. Emilie Hangen, et al. Interaction between AIF and CHCHD4 Regulates Respiratory Chain Biogenesis. Mol Cell. 2015 Jun 18;58(6):1001-14. [Content Brief]

[2]. Carlo Rinaldi, et al. Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. Am J Hum Genet. 2012 Dec 7;91(6):1095-102. [Content Brief]

[3]. Irina F Sevrioukova, et al. Structure/Function Relations in AIFM1 Variants Associated with Neurodegenerative Disorders. J Mol Biol. 2016 Sep 11;428(18):3650-65. [Content Brief]

[4]. Masato Mashimo, et al. The 89-kDa PARP1 cleavage fragment serves as a cytoplasmic PAR carrier to induce AIF-mediated apoptosis. J Biol Chem. 2021 Jan-Jun;296:100046. [Content Brief]

[5]. Daniele Ghezzi, et al. Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am J Hum Genet. 2010 Apr 9;86(4):639-49. [Content Brief]

[6]. Young-Ok Son, et al. Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Apoptosis. 2009 Jun;14(6):796-808. [Content Brief]

[7]. Cécile Delettre, et al. AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer. J Biol Chem. 2006 Mar 10;281(10):6413-27. [Content Brief]

[8]. Cécile Delettre, et al. Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity. J Biol Chem. 2006 Jul 7;281(27):18507-18. [Content Brief]

[9]. Jong-Tae Kim, et al. Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g). FEBS Lett. 2006 Nov 27;580(27):6375-83. [Content Brief]

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