Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductaseinvolved in apoptosis

Apoptosis-inducing factor (AIF) is encoded by one single gene located on th e X chromosome. AIF is ubiquitously expressed, both in normal tissues and i n a variety of cancer cell lines. The AIF precursor is synthesized in the c ytosol and is imported into mitochondria, The mature AIF protein, a flavopr otein (prosthetic group: flavine adenine dinucleotide) with significant hom ology to plant ascorbate reductases and bacterial NADH oxidases, is normall y confined to the mitochondrial intermembrane space. In a variety of differ ent apoptosis-inducing conditions, AIF translocates through the outer mitoc hondrial membrane to the cytosol and to the nucleus. Ectopic (extra-mitocho ndrial) AIP induces nuclear chromatin condensation, as well as large scale (similar to 50 kb) DNA fragmentation. Thus, similar to cytochrome c, AIF is a phylogenetically old, bifunctional protein with an electron acceptor/don or (oxidoreductase) function and a second apoptogenic function. In contrast to cytochrome c. however, AIF acts in a caspase-independent fashion. The m olecular mechanisms,ia which AIF induces apoptosis are discussed. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.