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Apoptosis-Inducing Factor: Structure, Function, and Redox Regulation

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Sevrioukova, Irina F.·2011·Antioxidants & Redox Signaling

Abstract

Apoptosis-inducing factor (AIF) is a flavin adenine dinucleotide-containing, NADH-dependent oxidoreductase residing in the mitochondrial intermembrane space whose specific enzymatic activity remains unknown. Upon an apoptotic insult, AIF undergoes proteolysis and translocates to the nucleus, where it triggers chromatin condensation and large-scale DNA degradation in a caspase-independent manner. Besides playing a key role in execution of caspase-independent cell death, AIF has emerged as a protein critical for cell survival. Analysis of in vivo phenotypes associated with AIF deficiency and defects, and identification of its mitochondrial, cytoplasmic, and nuclear partners revealed the complexity and multilevel regulation of AIF-mediated signal transduction and suggested an important role of AIF in the maintenance of mitochondrial morphology and energy metabolism. The redox activity of AIF is essential for optimal oxidative phosphorylation. Additionally, the protein is proposed to regulate the respiratory chain indirectly, through assembly and/or stabilization of complexes I and III. This review discusses accumulated data with respect to the AIF structure and outlines evidence that supports the prevalent mechanistic view on the apoptogenic actions of the flavoprotein, as well as the emerging concept of AIF as a redox sensor capable of linking NAD(H)-dependent metabolic pathways to apoptosis.

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Metadata

Authors
Sevrioukova, I. F.
Venue
Antioxidants & Redox Signaling
Published
2011-06-15
Volume
14
Issue
12
Pages
2545-2579
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W1965680695
Cited by
335
References
14
FWCI
3.31
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Apoptosis-Inducing Factor: Structure, Function, and Redox Regulation. https://app.cochat.ai/papers/10.1089/ars.2010.3445
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Sevrioukova, I. F. (2011). Apoptosis-Inducing Factor: Structure, Function, and Redox Regulation. Antioxidants & Redox Signaling. https://doi.org/10.1089/ars.2010.3445

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