Apoptosis-inducing factor: a matter of neuron life and death.
The mitochondrial flavoprotein apoptosis-inducing factor (AIF) is the main mediator of caspase-independent apoptosis-like programmed cell death. Upon pathological permeabilization of the outer mitochondrial membrane, AIF is translocated to the nucleus, where it participates in chromatin condensation and is associated to large-scale DNA fragmentation. Heavy down-regulation of AIF expression in mutant mice or reduced AIF expression achieved with small interfering RNA (siRNA) provides neuroprotection against acute neurodegenerative insults. Paradoxically, in addition to its pro-apoptotic function, AIF likely plays an anti-apoptotic role by regulating the production of reactive oxygen species (ROS) via its putative oxidoreductase and peroxide scavenging activities. In this review, we discuss accumulating evidence linking AIF to both acute and chronic neurodegenerative processes by emphasising mechanisms underlying the dual roles apparently played by AIF in these processes.
Krantic
Slavica
S
Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale, Parc Scientifique Luminy, BP13, 13 273 Marseille, France.
Mechawar
Naguib
N
Reix
Stéphanie
S
Quirion
Rémi
R
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology
D051033:Apoptosis Inducing Factor; D016166:Free Radical Scavengers