apoptosis inducing factor mitochondria associated 1
The information on this page was automatically extracted from online scientific databases.
From NCBI Gene:
This gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells, and it 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 affects chromosome condensation and fragmentation. In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Mutations in this gene cause combined oxidative phosphorylation deficiency 6 (COXPD6), a severe mitochondrial encephalomyopathy, as well as Cowchock syndrome, also known as X-linked recessive Charcot-Marie-Tooth disease-4 (CMTX-4), a disorder resulting in neuropathy, and axonal and motor-sensory defects with deafness and cognitive disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Aug 2015]
Has NADH oxidoreductase activity. Does not induce nuclear apoptosis.
Functions both as NADH oxidoreductase and as regulator of apoptosis (PubMed:20362274, PubMed:23217327, PubMed:17094969). 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. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA (By similarity). Binds to DNA in a sequence-independent manner (PubMed:27178839). Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis (PubMed:17094969). Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells (PubMed:19418225). 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 (PubMed:26004228).
Covered on Genetics Home Reference:
From NCBI Gene:
- Deafness, X-linked 5
- Cowchock syndrome
- Combined oxidative phosphorylation deficiency 6
- Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy
Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4): A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood. [MIM:310490]
Deafness, X-linked, 5 (DFNX5): 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. [MIM:300614]
Combined oxidative phosphorylation deficiency 6 (COXPD6): 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. [MIM:300816]
- OMIM: APOPTOSIS-INDUCING FACTOR, MITOCHONDRIA-ASSOCIATED, 1
- OMIM: CHARCOT-MARIE-TOOTH DISEASE, X-LINKED RECESSIVE, 4, WITH OR WITHOUT CEREBELLAR ATAXIA
- OMIM: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 6
- OMIM: DEAFNESS, X-LINKED 5, WITH PERIPHERAL NEUROPATHY
- OMIM: SPONDYLOEPIMETAPHYSEAL DYSPLASIA, X-LINKED, WITH HYPOMYELINATING LEUKODYSTROPHY