Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis.
Apoptosis-inducing factor (AIF) is encoded by one single gene located on the X chromosome. AIF is ubiquitously expressed, both in normal tissues and in a variety of cancer cell lines. The AIF precursor is synthesized in the cytosol and is imported into mitochondria. The mature AIF protein, a flavoprotein (prosthetic group: flavine adenine dinucleotide) with significant homology to plant ascorbate reductases and bacterial NADH oxidases, is normally confined to the mitochondrial intermembrane space. In a variety of different apoptosis-inducing conditions, AIF translocates through the outer mitochondrial membrane to the cytosol and to the nucleus. Ectopic (extra-mitochondrial) AIF induces nuclear chromatin condensation, as well as large scale ( approximately 50 kb) DNA fragmentation. Thus, similar to cytochrome c, AIF is a phylogenetically old, bifunctional protein with an electron acceptor/donor (oxidoreductase) function and a second apoptogenic function. In contrast to cytochrome c, however, AIF acts in a caspase-independent fashion. The molecular mechanisms via which AIF induces apoptosis are discussed.
Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, France.
E
E
Daugas
D
D
Nochy
L
L
Ravagnan
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M
Loeffler
S A
SA
Susin
N
N
Zamzami
G
G
Kroemer
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D018076:DNA, Complementary / Q000235:genetics; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014960:X Chromosome / Q000235:genetics
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D018076:DNA, Complementary; D005420:Flavoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D010088:Oxidoreductases