Apoptosis-inducing factor: a matter of neuron life and death |
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| Authors: | Krantic Slavica Mechawar Naguib Reix Stéphanie Quirion Rémi |
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| Affiliation: | Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale, Parc Scientifique Luminy, BP13, 13 273 Marseille, France. |
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| Abstract: | ![]()
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. |
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| Keywords: | AD, Alzheimer's disease ADP, adenosine diphosphate AIF, apoptosis-inducing factor AIP-1, ALG-2-interacting protein-1 ALG-2, apoptosis-linked gene-2 Alix, ALG-2-interacting protein X AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid Apaf1, apoptosis protease activation factor-1 APP, amyloid precursor protein ATP, adenosine triphosphate Aβ, amyloid beta Bak, Bcl-2 homologous antagonist/killer Bax, Bcl-2-associated X protein Bcl-2, B-cell leukemia 2 BrdU, 5-Bromo-2-deoxyUridine CAD, caspase activated DNase CD95, common determinant 95 CD95L, CD95 ligand C-terminal, COOH-terminal DCR, DeCoy receptor DD, death domains DED, death effector domains DIABLO, direct IAP binding protein of low pI DISC, death-inducing signaling complex DNA, deoxyribonucleic acid DNase, DNA ladder nuclease EGF, epidermal growth factor EGFR, epidermal growth factor receptor Endo G, endonuclease G FAD, flavine adenine dinucleotide FADD, fas-associated death domain FADH2, reduced flavine adenine dinucleotide FasL, fas ligand GP, glutathione-peroxidase GSSG, glutathione disulfide H2O2, hydrogen peroxide Hq, harlequin Hsp70, heat shock protein 70 kDa HtrA2/OMI, high temperature requirement protein A2 IAP, inhibitor of apoptosis protein ICAD, inhibitor of CAD IGFR-I, insulin-like growth factor receptor I kDa, kiloDalton L-DNase II, leucocyte-derived DNase II MAPK, mitogen-activated protein kinase MLS, mitochondrial localization sequences mM-CSF, macrophage colony-stimulating factor MOMP, mitochondrial outer membrane permeabilization MPP+, 1-methyl-4-phenylpyridine MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mRNA, messenger ribonucleic acid NADH/NAD, nicotinamide adenine dinucleotide NAIP, neuronal apoptosis inhibitory protein NLS, nuclear localization sequence NMDA, N-methyl-d-aspartate NO, nitric oxide N-terminal, NH2-terminal O2•−, superoxide anion OH•, hydroxyl radical ONOO−, peroxynitrite OPG, osteoprotegerin PAR, poly(ADP-ribose) PARP-1, poly(ADP-ribose) polymerase-1 PC12, rat adrenal pheochromocytoma cells PCD, programmed cell death PD, Parkinson's disease Q-VD-OPh, N-(2-quinolyl)valyl-aspartyl-(2,6-difluorophenoxy)methyl ketone RAIDD, RIP-associated ICH-1 homologous protein with a death domain ROS, reactive oxygen species siRNA, small interfering RNA Smac, second mitochondrial activator of caspase SIRT1, Sirtin-1 SOD, superoxide dismutase TNF, tumor necrosis factor TNF-R, tumor necrosis factor receptor TRADD, TNF-R1-associated death domain TRAIL, TNF-related apoptosis-inducing ligand TRAIL-R, TNF-related apoptosis-inducing ligand receptor TRAMP, transgenic adenocarcinoma of the mouse prostate TWEAK, TNF-like WEAK UCP, mitochondrial uncoupling proteins VDAC, voltage-dependent anion channel Z-VAD-fmk, benzyloxycarbonyl-VAD-fluoromethylketone ΔΨm, mitochondrial transmembrane potential |
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