AIFM1

GeneName

AIFM1

Summary

AIFM1, also known as AIF, is a 67 kDa protein that is primarily localised to the mitochondrion, particularly within the mitochondrial inner membrane and intermembrane space, but is also found in the cytoplasm and nucleus. It plays a vital role in various cellular processes, including the intrinsic apoptotic pathway, where it is involved in the translocation to the nucleus during apoptosis. AIFM1 exhibits multiple molecular functions such as DNA binding, FAD binding, and NADH dehydrogenase activity, contributing to its role in oxidative stress response and mitochondrial function. Additionally, it is implicated in processes such as neuronal differentiation and the cellular response to various stimuli including estradiol and hydrogen peroxide.

Importance

AIFM1 is relevant to: - Apoptosis and cell death regulation, particularly in the context of neurodegenerative diseases and cancer - Mitochondrial function and oxidative stress response, which are crucial in metabolic disorders - Neuronal health, given its role in neuron differentiation and responses to ischemia and toxic substances - Potential therapeutic targets for diseases associated with mitochondrial dysfunction and apoptosis dysregulation

Top Products

For researchers investigating AIFM1, we highly recommend the top-selling recombinant monoclonal antibody, Anti-AIF antibody [E20] - Mitochondrial Marker (ab32516). This antibody has been validated in knockout models, ensuring its reliability for your experiments. It is suitable for a variety of applications, including Western blotting (WB), immunocytochemistry (ICC), immunohistochemistry (IHC), immunoprecipitation (IP), and flow cytometry (FC). With 91 citations, this antibody is well-regarded in the research community, making it an excellent choice for those studying AIFM1. The Complex I Human Protein Quantity Dipstick Assay Kit (ab109722) is a reliable option for researchers looking to measure AIFM1, supported by 8 citations.

Abcam Product Citation Summary

The data indicates that AIFM1 is being studied in various contexts, particularly in relation to mitochondrial dysfunction, oxidative stress, and heart failure. The use of both Western blotting and immunocytochemistry in rat cardiomyocytes highlights the importance of this target in cardiac studies. Additionally, research involving human ovarian cancer cells and chronic obstructive sleep apnoea in dogs suggests a broader relevance of AIFM1 across different species and conditions.

Abcam Product Citation Table

Function

Functions both as NADH oxidoreductase and as regulator of apoptosis (PubMed:17094969, PubMed:20362274, PubMed:23217327, PubMed:33168626). 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 (PubMed:20362274). 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 (PubMed:20362274). 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).

Isoform 4

Has NADH oxidoreductase activity. Does not induce nuclear apoptosis.

Isoform 5

Pro-apoptotic isoform.

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Deafness, X-linked, 5, with peripheral neuropathy

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy

SEMDHL

An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-255 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death.

Sequence Similarities

Belongs to the FAD-dependent oxidoreductase family.

Tissue Specificity

Expressed in all tested tissues (PubMed:16644725). Detected in muscle and skin fibroblasts (at protein level) (PubMed:23217327). Expressed in osteoblasts (at protein level) (PubMed:28842795).

Isoform 3

Brain specific.

Isoform 4

Expressed in all tested tissues except brain.

Isoform 5

Isoform 5 is frequently down-regulated in human cancers.

Cellular localization

• 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 (PubMed:15775970). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (By similarity). Translocation into the nucleus is promoted by interaction with (auto-poly-ADP-ribosylated) processed form of PARP1 (PubMed:33168626). Colocalizes with EIF3G in the nucleus and perinuclear region (PubMed:17094969).
• Isoform 3
• Mitochondrion intermembrane space
• Mitochondrion inner membrane
• Has a stronger membrane anchorage than isoform 1.
• Isoform 4
• Mitochondrion
• Cytoplasm
• Cytosol
• In pro-apoptotic conditions, is released from mitochondria to cytosol in a calpain/cathepsin-dependent manner.
• Isoform 5
• Cytoplasm

Alternative names

AIF, PDCD8, AIFM1, Programmed cell death protein 8

Database links

swissprot:O95831 omim:300169 entrezGene:9131 entrezGene:51060