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AIF 6C4 Monoclonal Antibody

Info

Catalogue Number 154126
Applications WB
Antigen/Gene or Protein Targets Mammalian Apoptosis-Inducing Factor (AIF)
Reactivity Mouse
Host Mouse
Immunogen AIF-His fusion protein
Subclass IgG1
Recommended Growing Conditions Aliquot and store antibodies at -20C for prolonged usage
Notes Mammalian apoptosis-inducing factor (AIF) has been reported to be mainly found in the inter-membrane space of the mitochondria. After exposure to apoptotic stimuli, AIF is expelled as a soluble protein from the permeabilised mitochondria membrane and translocates to the nucleus, resulting in chromatin condensation and DNA cleavage. AIF mediated apoptosis is caspase-independent. AIF mutants that could not bind to DNA could not mediate cell death. Therefore, it follows that additional factor/s is required for hallmarks of apoptosis to occur. Indeed, in C. elegans, the homologue WAH-1 binds to mammalian endonuclease G homologue, CPS6. However, no such equivalent was found in mammalian cells.

In the studies of excitotoxicity, the N-methyl D-aspartate (NDMA) is excessively activated for glutamate, triggering calcium influx to activate nitric oxide (NO) synthase. NO would react to superoxide O¬2-, forming ONOO- resulting in ROS-mediated damages, involving PARP-1. This process also involves AIF release from mitochondria and nuclear translocation in PARP-1 dependent manner of which the precise mechanism is not known. The limited evidence of such observation leads to speculation on the role of AIF as proapoptotic in cellular insults and injury.

Nonetheless, a paradox is observed in the increasing evidence that AIF have a pro-survival role in mammalian development and normal homeostasis. Knock-out of AIF in mouse is lethal before birth. AIF-deficient human carcinoma or AIF-null ES cells showed high lactate production and enhanced dependence on glycolytic generation of ATP. This is due to decreased complex I protein synthesis or assembly. Therefore AIF is speculated to have an unknown role in the former because though it is located near or within the inner mitochondrial membrane where oxidative phosphorylation occurs, it does not co-purify with complex I.

It has been observed than in harlequin a (Hq) mutant mouse, which has more than 80% reduction AIF protein, oxidative stress is involved in neurodegeneration. Oxidative stress could be due to the reduction of complex I activity. This would result in increased premature diversion of electrons at complex I into molecular oxygen to form O2- which subsequently dismutate to H2O2. It remains unknown how AIF suppresses oxidative stress since AIF catalyses O2- in vitro.

AIF also seemed to affect the formation of cytoplasmic stress granules (SG). Indirectly, knock out of AIF in ES cells and HeLa cells enhanced formation of SG induced by arsenate. AIF mutants which lack mitochondrial targeting sequence or NADH-binding activity did not suppress SG formation. Supplementation of AI-deficient cells with GSH restored the suppression of SG because marked attenuation of NAD(P)H oxidation and increased GSH depletion. It should be noted that while the former restored regulation of SG, complex I activity is not restored, implicating AIF works in different ways involving both events.
Research Area Apoptosis and Programmed Cell Death, Cell Cycle, Other

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