Genomes and Genes
apoptosis inducing factor
Summary: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
- Mader J, Mookherjee N, Hancock R, Bleackley R. The human host defense peptide LL-37 induces apoptosis in a calpain- and apoptosis-inducing factor-dependent manner involving Bax activity. Mol Cancer Res. 2009;7:689-702 pubmed publisher..Together, these data show that LL-37-induced apoptosis is mediated via the mitochondria-associated pathway in a caspase-independent and calpain- and AIF-dependent manner that involves Bax activation and translocation to mitochondria. ..
- Joza N, Pospisilik J, Hangen E, Hanada T, Modjtahedi N, Penninger J, et al. AIF: not just an apoptosis-inducing factor. Ann N Y Acad Sci. 2009;1171:2-11 pubmed publisher..Here, we discuss the manifold nature of AIF in cell life and death, with particular emphasis of its roles in vivo. ..
- Burguillos M, Hajji N, Englund E, Persson A, Cenci A, Machado A, et al. Apoptosis-inducing factor mediates dopaminergic cell death in response to LPS-induced inflammatory stimulus: evidence in Parkinson's disease patients. Neurobiol Dis. 2011;41:177-88 pubmed publisher..We also observed nuclear translocation of AIF in the ventral mesencephalon of Parkinson's disease subjects. ..
- Chung S, Calafiore M, Plane J, Pleasure D, Deng W. Apoptosis inducing factor deficiency causes reduced mitofusion 1 expression and patterned Purkinje cell degeneration. Neurobiol Dis. 2011;41:445-57 pubmed publisher..Alteration in mitochondrial dynamics has been implicated in many neurodegenerative diseases. Mitochondrial apoptosis inducing factor (AIF) plays a key role in multiple cellular and disease processes...
- Wang Y, Kim N, Li X, Greer P, Koehler R, Dawson V, et al. Calpain activation is not required for AIF translocation in PARP-1-dependent cell death (parthanatos). J Neurochem. 2009;110:687-96 pubmed publisher..Our study clearly shows that calpain activation is not required for AIF release during parthanatos, suggesting that other mechanisms rather than calpain are involved in mitochondrial AIF release in parthanatos. ..
- Schulthess F, Katz S, Ardestani A, Kawahira H, Georgia S, Bosco D, et al. Deletion of the mitochondrial flavoprotein apoptosis inducing factor (AIF) induces beta-cell apoptosis and impairs beta-cell mass. PLoS ONE. 2009;4:e4394 pubmed publisher..A key mediator of apoptosis, mitochondrial function, and cell survival is apoptosis inducing factor (AIF)...
- Polster B. AIF, reactive oxygen species, and neurodegeneration: a "complex" problem. Neurochem Int. 2013;62:695-702 pubmed publisher..It also discusses the controversial role of complex I deficiency in Parkinson's disease, and what can be learned from the AIF- and complex I-depleted harlequin mouse. ..
- Chaitanya G, Babu P. Multiple apoptogenic proteins are involved in the nuclear translocation of Apoptosis Inducing Factor during transient focal cerebral ischemia in rat. Brain Res. 2008;1246:178-90 pubmed publisherb>Apoptosis Inducing Factor is a mitochondrial protein which upon translocation to nucleus causes large scale DNA fragmentation...
- Li S, Yu W, Hu G. Angiogenin inhibits nuclear translocation of apoptosis inducing factor in a Bcl-2-dependent manner. J Cell Physiol. 2012;227:1639-44 pubmed publisher..Here we report that ANG inhibits nuclear translocation of apoptosis inducing factor (AIF), an important cell death-executing molecule known to play a dominant role in neurodegenerative ..
- Zhuang Y, Miskimins W. Metformin induces both caspase-dependent and poly(ADP-ribose) polymerase-dependent cell death in breast cancer cells. Mol Cancer Res. 2011;9:603-15 pubmed publisher..Thus, metformin has cytotoxic effects on breast cancer cells through 2 independent pathways. These findings will be pertinent to efforts directed at using metformin or related compounds for cancer therapy. ..
- Thal S, Zhu C, Thal S, Blomgren K, Plesnila N. Role of apoptosis inducing factor (AIF) for hippocampal neuronal cell death following global cerebral ischemia in mice. Neurosci Lett. 2011;499:1-3 pubmed publisher..In AIF(low) mice neuronal cell loss was reduced by 60% (p<0.02). The current experiments suggest that AIF-mediated signaling represents a novel mechanism of neuronal cell death following GCI. ..
- Artus C, Boujrad H, Bouharrour A, Brunelle M, Hoos S, Yuste V, et al. AIF promotes chromatinolysis and caspase-independent programmed necrosis by interacting with histone H2AX. EMBO J. 2010;29:1585-99 pubmed publisher..Overall, our data shed new light in the mechanisms regulating programmed necrosis, elucidate a key nuclear partner of AIF, and uncover an AIF apoptogenic motif. ..
- Brust D, Hamann A, Osiewacz H. Deletion of PaAif2 and PaAmid2, two genes encoding mitochondrial AIF-like oxidoreductases of Podospora anserina, leads to increased stress tolerance and lifespan extension. Curr Genet. 2010;56:225-35 pubmed publisher..These data identify components of a caspase-independent molecular pathway to be involved in developmental processes and in the induction of programmed cell death in the senescent stage of P. anserina...
- Zhao Y, Wang J, Fu B, Ma M, Li B, Huang Q, et al. Effects of 3-aminobenzamide on expressions of poly (ADP ribose) polymerase and apoptosis inducing factor in cardiomyocytes of rats with acute myocardial infarction. Chin Med J (Engl). 2009;122:1322-7 pubmed..were noted, PARP cleavage was measured by Western blotting, and expressions of protein of PARP and apoptosis inducing factor (AIF) were measured by immunohistochemical staining after treatment with 3-AB for 2 hours, 4 hours, 6 ..
- Wang Y, Kim N, Haince J, Kang H, David K, Andrabi S, et al. Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci Signal. 2011;4:ra20 pubmed publisher..Interference with the PAR-AIF interaction or PAR signaling may provide notable opportunities for preventing cell death after activation of PARP-1. ..
- Sun Y, Zhang Y, Wang X, Blomgren K, Zhu C. Apoptosis-inducing factor downregulation increased neuronal progenitor, but not stem cell, survival in the neonatal hippocampus after cerebral hypoxia-ischemia. Mol Neurodegener. 2012;7:17 pubmed publisher..These findings demonstrate that AIF downregulation provides not only long-term overall neuroprotection after HI, but also protects neural progenitor cells, thereby rescuing hippocampal neurogenesis. ..
- Baritaud M, Boujrad H, Lorenzo H, Krantic S, Susin S. Histone H2AX: The missing link in AIF-mediated caspase-independent programmed necrosis. Cell Cycle. 2010;9:3166-73 pubmed..In the present article, we outline the current knowledge on cell death by programmed necrosis and discuss the relevance of the AIF/H2AX/CypA DNA-degrading complex in the regulation of this original form of cell death. ..
- Zhang J, Sun B, Huang Y, Kouadir M, Zhou X, Wang Y, et al. IFN-? promotes THP-1 cell apoptosis during early infection with Mycobacterium bovis by activating different apoptotic signaling. FEMS Immunol Med Microbiol. 2010;60:191-8 pubmed publisher..0% in untreated cells. Taken together, these results suggest that IFN-? promotes apoptosis of M. bovis-infected THP-1 cells during early infection through the TNF-?-mediated death receptor and the AIF apoptotic pathway. ..
- Vosler P, Sun D, Wang S, Gao Y, Kintner D, Signore A, et al. Calcium dysregulation induces apoptosis-inducing factor release: cross-talk between PARP-1- and calpain-signaling pathways. Exp Neurol. 2009;218:213-20 pubmed publisher..Collectively, these findings link the two seemingly independent mechanisms triggering AIF-induced neuronal death. ..
- Norberg E, Gogvadze V, Vakifahmetoglu H, Orrenius S, Zhivotovsky B. Oxidative modification sensitizes mitochondrial apoptosis-inducing factor to calpain-mediated processing. Free Radic Biol Med. 2010;48:791-7 pubmed publisher..Combined, our data provide evidence that ROS-mediated, posttranslational modification of AIF is critical for its cleavage by calpain and thus for AIF-mediated cell death. ..
- Ferreira P, Villanueva R, Cabon L, Susin S, Medina M. The oxido-reductase activity of the apoptosis inducing factor: a promising pharmacological tool?. Curr Pharm Des. 2013;19:2628-36 pubmedThe apoptosis inducing factor (AIF) was first discovered as a caspase-independent apoptosis effector that promoted cell death upon release from the mitochondria (triggered by pro-apoptotic stimuli) and relocalization into the nucleus, ..
- Berger I, Ben Neriah Z, Dor Wolman T, Shaag A, Saada A, Zenvirt S, et al. Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing. Mol Genet Metab. 2011;104:517-20 pubmed publisher..In summary, linkage analysis followed by exome sequencing of a single patient is a cost-effective approach for the identification of disease causing mutations in small non-consanguineous families. ..
- Hangen E, Blomgren K, Benit P, Kroemer G, Modjtahedi N. Life with or without AIF. Trends Biochem Sci. 2010;35:278-87 pubmed publisher..Mice that express reduced levels of AIF constitute a reliable model of complex I deficiency. Here we discuss recent reports on the survival-related function(s) of AIF. ..
- Mizukoshi S, Nakazawa M, Sato K, Ozaki T, Metoki T, Ishiguro S. Activation of mitochondrial calpain and release of apoptosis-inducing factor from mitochondria in RCS rat retinal degeneration. Exp Eye Res. 2010;91:353-61 pubmed publisher..The present study provides new insights into the molecular basis for photoreceptor apoptosis in RCS rats and the future possibility of new pharmaceutical treatments for retinitis pigmentosa...
- Banerjee H, Das A, Srivastava S, Mattoo H, Thyagarajan K, Khalsa J, et al. A role for apoptosis-inducing factor in T cell development. J Exp Med. 2012;209:1641-53 pubmed publisher..Thus, Aif, a ubiquitous protein, serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic ?-selection...
- Lu J, Lu W, Lai J, Tsai F, Wu S, Lin C, et al. Calcium flux and calpain-mediated activation of the apoptosis-inducing factor contribute to enterovirus 71-induced apoptosis. J Gen Virol. 2013;94:1477-85 pubmed publisher..These findings should be useful for understanding the virus-induced cytopathology and the impact of Ca²? homeostasis on EV71 infection. ..
- Lewis E, Wilkinson A, Davis N, Horita D, Wilkinson J. Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation. Biochemistry. 2011;50:11084-96 pubmed publisherb>Apoptosis inducing factor (AIF) is a mediator of caspase-independent cell death that is also necessary for mitochondrial energy production. How these seemingly opposite cellular functions of AIF are controlled is poorly understood...
- Delavallée L, Cabon L, Galán Malo P, Lorenzo H, Susin S. AIF-mediated caspase-independent necroptosis: a new chance for targeted therapeutics. IUBMB Life. 2011;63:221-32 pubmed publisher..We also summarize the state of the art in some of the most interesting therapeutic strategies that could target AIF or the AIF-mediated necroptotic pathway. ..
- Bajt M, Ramachandran A, Yan H, Lebofsky M, Farhood A, Lemasters J, et al. Apoptosis-inducing factor modulates mitochondrial oxidant stress in acetaminophen hepatotoxicity. Toxicol Sci. 2011;122:598-605 pubmed publisher..Thus, AIF has a critical function in APAP hepatotoxicity by facilitating generation of reactive oxygen in mitochondria and, after nuclear translocation, AIF can be involved in DNA fragmentation. ..
- Cabon L, Galán Malo P, Bouharrour A, Delavallée L, Brunelle Navas M, Lorenzo H, et al. BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation. Cell Death Differ. 2012;19:245-56 pubmed publisher..Altogether, our data reveal that, as in caspase-dependent apoptosis, BH3-only proteins are key regulators of caspase-independent necroptosis. ..
- Kunte M, Choudhury S, Manheim J, Shinde V, Miura M, Chiodo V, et al. ER stress is involved in T17M rhodopsin-induced retinal degeneration. Invest Ophthalmol Vis Sci. 2012;53:3792-800 pubmed publisher..The final demise of photoreceptors occurs via apoptosis involving ER stress-associated and mitochondria-induced caspase activation. We identified Atg5, Atg7, Bax, Bid, Bik, and Noxa as potential therapeutic targets for adRP treatment. ..
- Perez Alvarez S, Iglesias Guimarais V, Solesio M, Melero Fernandez de Mera R, Yuste V, Galindo M, et al. Methadone induces CAD degradation and AIF-mediated necrotic-like cell death in neuroblastoma cells. Pharmacol Res. 2011;63:352-60 pubmed publisher..However, the downstream mitochondrial pathways remained unclear. Here, we studied the participation of apoptosis inducing factor (AIF) in methadone-induced cell death...
- Ozaki T, Yamashita T, Ishiguro S. Mitochondrial m-calpain plays a role in the release of truncated apoptosis-inducing factor from the mitochondria. Biochim Biophys Acta. 2009;1793:1848-59 pubmed publisher..Our results demonstrated that mitochondrial m-calpain plays a role in the release of tAIF from mitochondria by cleaving VDAC, and tAIF is released through VDAC-Bax pores. ..
- Liu L, Xing D, Chen W. Micro-calpain regulates caspase-dependent and apoptosis inducing factor-mediated caspase-independent apoptotic pathways in cisplatin-induced apoptosis. Int J Cancer. 2009;125:2757-66 pubmed publisher..calpain activation, as measured by a fluorescent substrate, was an early event, taking place well before apoptosis inducing factor (AIF) release and caspase-9/-3 activation...
- Chinta S, Rane A, Yadava N, Andersen J, Nicholls D, Polster B. Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria. Free Radic Biol Med. 2009;46:939-47 pubmed..These findings raise the important possibility that complex I contributes less to physiological ROS production by brain mitochondria than previously suggested. ..
- Ashktorab H, Dashwood R, Dashwood M, Zaidi S, Hewitt S, Green W, et al. H. pylori-induced apoptosis in human gastric cancer cells mediated via the release of apoptosis-inducing factor from mitochondria. Helicobacter. 2008;13:506-17 pubmed publisher..pylori. Hence, the balance between apoptosis and proliferation in these cells may be altered in response to injury caused by H. pylori infection, leading to an increased risk of cancer. ..
- Skyrlas A, Hantschke M, Passa V, Gaitanis G, Malamou Mitsi V, Bassukas I. Expression of apoptosis-inducing factor (AIF) in keratoacanthomas and squamous cell carcinomas of the skin. Exp Dermatol. 2011;20:674-6 pubmed publisher..01). These findings indicate to a distinctive involvement of AIF in the progression of certain epithelial skin tumors that might be exploited as a promising treatment target. ..
- Osato K, Sato Y, Ochiishi T, Osato A, Zhu C, Sato M, et al. Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation. Cell Death Dis. 2010;1:e84 pubmed publisher..Together, these results indicate that targeting AIF may provide a fruitful strategy for protection of normal brain tissue against the detrimental side effects of IR. ..
- Zhou Y, Feng X, Koh D. Activation of cell death mediated by apoptosis-inducing factor due to the absence of poly(ADP-ribose) glycohydrolase. Biochemistry. 2011;50:2850-9 pubmed publisher..Therefore, the absence of PARG may provide a strategy for specifically inducing an alternative apoptotic pathway. ..
- Armand A, Laziz I, Djeghloul D, Lecolle S, Bertrand A, Biondi O, et al. Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype. PLoS ONE. 2011;6:e27283 pubmed publisherb>Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress...
- Norberg E, Orrenius S, Zhivotovsky B. Mitochondrial regulation of cell death: processing of apoptosis-inducing factor (AIF). Biochem Biophys Res Commun. 2010;396:95-100 pubmed publisher..The current knowledge about the molecular mechanisms regulating the processing and release of AIF from the mitochondria will be summarized and discussed in this review. ..
- Gao H, Zheng W, Xin N, Chi Z, Wang Z, Chen J, et al. Zinc deficiency reduces neurogenesis accompanied by neuronal apoptosis through caspase-dependent and -independent signaling pathways. Neurotox Res. 2009;16:416-25 pubmed publisher..Meanwhile, the apoptosis proteins, including Fas, Fas ligand (FasL), apoptosis inducing factor (AIF), and caspase-3, were significantly activated in zinc-deficient mouse hippocampus...
- Wang Y, Dawson V, Dawson T. Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol. 2009;218:193-202 pubmed publisher..Targeting PAR-mediated AIF release could be a potential approach for the therapy of neurologic disorders. ..
- Wang X, Carlsson Y, Basso E, Zhu C, Rousset C, Rasola A, et al. Developmental shift of cyclophilin D contribution to hypoxic-ischemic brain injury. J Neurosci. 2009;29:2588-96 pubmed publisher..The role of CypD in HI shifts from a predominantly prosurvival protein in the immature to a cell death mediator in the adult brain. ..
- García Cáceres C, Lechuga Sancho A, Argente J, Frago L, Chowen J. Death of hypothalamic astrocytes in poorly controlled diabetic rats is associated with nuclear translocation of apoptosis inducing factor. J Neuroendocrinol. 2008;20:1348-60 pubmed publisher..By contrast, nuclear translocation of apoptosis inducing factor (AIF) increased significantly in astrocytes in parallel with the increase in death and AIF was found in ..
- Piao C, Loane D, Stoica B, Li S, Hanscom M, Cabatbat R, et al. Combined inhibition of cell death induced by apoptosis inducing factor and caspases provides additive neuroprotection in experimental traumatic brain injury. Neurobiol Dis. 2012;46:745-58 pubmed publisher..caspase-dependent and caspase-independent mechanisms have been implicated, with the latter including apoptosis inducing factor (AIF)...
- Fan T, Tian F, Yi S, Ke Y, Han S, Zhang L, et al. Implications of Bit1 and AIF overexpressions in esophageal squamous cell carcinoma. Tumour Biol. 2014;35:519-27 pubmed publisher..05). Correctively, our data cited earlier suggest that Bit1 plays pivotal roles in the development and progression of ESCC, and its biological functions in ESCC may be closely associated with AIF and Bcl-2 levels. ..