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Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis Daugas E; Nochy D; Ravagnan L; Loeffler M; Susin SA; Zamzami N; Kroemer GFEBS Lett 2000[Jul]; 476 (3): 118-23Apoptosis-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.|Animals[MESH]|Apoptosis Inducing Factor[MESH]|Apoptosis/drug effects/*physiology[MESH]|DNA, Complementary/genetics[MESH]|Flavoproteins/genetics/*metabolism/pharmacology[MESH]|Gene Expression[MESH]|Humans[MESH]|Membrane Proteins/genetics/*metabolism/pharmacology[MESH]|Mitochondria/*metabolism[MESH]|Oxidoreductases/genetics/*metabolism[MESH]|RNA, Messenger/genetics/metabolism[MESH]|Tissue Distribution[MESH]|X Chromosome/genetics[MESH] |
