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Title: Redox-dependent changes in molecular properties of mitochondrial apoptosis-inducing factor. Author: Churbanova IY, Sevrioukova IF. Journal: J Biol Chem; 2008 Feb 29; 283(9):5622-31. PubMed ID: 18167347. Abstract: Mitochondrial apoptosis-inducing factor (AIF) is a central player in the caspase-independent cell death pathway whose normal physiological function remains unclear. Our study showed that naturally folded mouse AIF very slowly reacts with NAD(P)H (k cat of 0.2-0.01 s(-1)) forming tight, dimeric, and air-stable FADH2-NAD(P) charge-transfer complexes ineffective in electron transfer. FAD reduction is accompanied by a conformational change involving AIF-specific N-terminal and regulatory 509-559 peptides and the active site His 453, and it affects susceptibility of AIF to calpain and AIF-DNA interaction, the two events critical for initiating caspase-independent apoptosis. Based on our results, we propose that formation of long lived complexes with NAD(P)H and redox reorganization may be functionally important and enable AIF to act as a redox-signaling molecule linking NAD(P)H-dependent metabolic pathways to apoptosis.[Abstract] [Full Text] [Related] [New Search]