| Function: |
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. In contrast, functions as an antiapoptotic factor in normal mitochondria via its NADH oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis, and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner. |
| Tissue Specificity: |
Detected in muscle and skin fibroblasts (at protein level). Isoform 5 is frequently down-regulated in human cancers. |
| Involvement in Disease: |
Combined oxidative phosphorylation deficiency 6: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy.
Cowchock syndrome: An X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment.
Deafness, X-linked, 5: A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system. |
| Sequence Similarities: |
Belongs to the FAD-dependent oxidoreductase family. |
| Post-Translational Modification: |
Under normal conditions, a 54-residue N-terminal segment is first proteolytically removed during or just after translocation into the mitochondrial intermembrane space (IMS) by the mitochondrial processing peptidase (MPP) to form the inner-membrane-anchored mature form (AIFmit). During apoptosis, it is further proteolytically processed at amino-acid position 101 leading to the generation of the mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis in a caspase-independent manner. |
| Cellular Location: |
Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Cytoplasm > Perinuclear region.
Proteolytic cleavage during or just after translocation into the mitochondrial intermembrane space (IMS) results in the formation of an inner-membrane-anchored mature form (AIFmit). During apoptosis, further proteolytic processing leads to a mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis. Colocalizes with EIF3G in the nucleus and perinuclear region. |
| Database Links: |
Entrez Gene: 51060?HumanEntrez Gene: 9131?HumanEntrez Gene: 26926?MouseEntrez Gene: 83533?RatOmim: 300169?HumanSwissProt: O95831?HumanSwissProt: Q9Z0X1?MouseSwissProt: Q9JM53?RatUnigene: 424932?HumanUnigene: 476033?HumanUnigene: 240434?MouseUnigene: 203165?Rat |
| Synonyms: |
AIF AntibodyAIFM1 AntibodyAIFM1_HUMAN AntibodyAIFsh2 AntibodyApoptosis inducing factor AntibodyApoptosis inducing factor 1, mitochondrial AntibodyApoptosis inducing factor, mitochondrion associated, 1 AntibodyApoptosis-inducing factor AntibodyApoptosis-inducing factor 1 AntibodyApoptosis-inducing factor 1, mitochondrial AntibodyApoptosis-inducing factor, mitochondrion-associated, 1 AntibodyCMTX4 AntibodyCOWCK AntibodyCOXPD6 AntibodyHarlequin AntibodyHq AntibodymAIF AntibodyMGC111425 AntibodyMGC5706 Antibodymitochondrial AntibodyNeuropathy, axonal motor-sensory, with deafness and mental retardation Antibodyneuropathy, axonal, motor-sensory with deafness and mental retardation (Cowchock syndrome) AntibodyPDCD 8 AntibodyPDCD8 AntibodyProgrammed cell death 8 AntibodyProgrammed cell death 8 (apoptosis inducing factor) AntibodyProgrammed cell death 8 isoform 1 AntibodyProgrammed cell death 8 isoform 2 AntibodyProgrammed cell death 8 isoform 3 AntibodyProgrammed cell death protein 8 AntibodyProgrammed cell death protein 8 mitochondrial AntibodyProgrammed cell death protein 8 mitochondrial precursor AntibodyStriatal apoptosis inducing factor Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
