Preferred Label : AIF Pathway;
NCIt related terms : Opposing roles of AIF in Apoptosis and Cell Survival;
Alternative definition : BIOCARTA: Programmed cell death is induced by many different factors and involves
numerous signaling pathways, some dependent on caspase proteases and others that are
caspase independent. Like cytochrome C, AIF (apoptosis-inducing factor) is a protein
found in mitochondria that is released from mitochondria by apoptotic stimuli. While
cytochrome C is linked to caspase-dependent apoptotic signaling, AIF release stimulates
caspase-independent apoptosis, moving into the nucleus where it binds DNA. DNA binding
by AIF stimulates chromatin condensation, and DNA fragmentation, perhaps through recruitment
of nucleases. DNA-binding by AIF occurs through a distinct domain of the protein in
a manner that does not rely on specific DNA sequences. AIF also has another domain
that acts as an NADH oxidase, a redox enzyme. The NADH oxidase activity of AIF is
separable from its DNA-binding activity and is not required for AIF to induce apoptosis.
In this role, AIF protects against apoptosis rather than inducing apoptosis. In mice
down regulation of the AIF gene created harlequin mice with oxidative damage to neurons
and increased neuronal cell death. Loss of AIF also increased sensitivity to peroxides,
suggesting that AIF may act as a peroxide scavenger. The mechanism by which AIF protects
against peroxide damage is not clear, but may involve a more indirect mechanism than
direct peroxide scavenging since the enzyme does not appear to have this activity
in vitro. Elucidating further the role of AIF as a redox enzyme will shed further
light on its normal function in mitochondria as well as its role in apoptosis and
disease. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_aifPathway;
Origin ID : C38977;
UMLS CUI : C1515839;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
