Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity - PubMed (original) (raw)
. 2006 Jul 7;281(27):18507-18.
doi: 10.1074/jbc.M601751200. Epub 2006 Apr 27.
Affiliations
- PMID: 16644725
- DOI: 10.1074/jbc.M601751200
Free article
Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity
Cécile Delettre et al. J Biol Chem. 2006.
Free article
Abstract
Apoptosis-inducing factor (AIF) is a bifunctional NADH oxidase involved in mitochondrial respiration and caspase-independent apoptosis. Three alternatively spliced mRNA isoforms of AIF have been identified previously: AIF, AIF-exB, and AIFsh. Here, we report the cloning and the biochemical characterization of a new isoform named AIF short 2 (AIFsh2). AIFsh2 transcript includes a previously unknown exon placed between exons 9 and 10 of AIF. The resulting AIFsh2 protein, which localizes in mitochondria, corresponds to the oxidoreductase domain of AIF. In this way, AIFsh2 exhibits similar NADH oxidase activity to AIF and generates reactive oxygen species. Like AIF, AIFsh2 is released from mitochondria to cytosol after an apoptotic insult in a calpain or cathepsin-dependent manner. However, in contrast to AIF, AIFsh2 does not induce nuclear apoptosis. Thus, it seems that the reactive oxygen species produced by the oxidoreductase domain of AIF/AIFsh2 are not important for AIF-dependent nuclear apoptosis. In addition, we demonstrate that the AIFsh2 mRNA is absent in normal brain tissue, whereas it is expressed in neuroblastoma-derived cells, suggesting a different regulation in normal and transformed cells from the brain lineage. Together, our results reveal that AIF yields an original and independent genetic regulation of the two AIF functions. This is an important issue to understand the physiological role of this protein.
Similar articles
- AIF3 splicing switch triggers neurodegeneration.
Liu S, Zhou M, Ruan Z, Wang Y, Chang C, Sasaki M, Rajaram V, Lemoff A, Nambiar K, Wang JE, Hatanpaa KJ, Luo W, Dawson TM, Dawson VL, Wang Y. Liu S, et al. Mol Neurodegener. 2021 Apr 14;16(1):25. doi: 10.1186/s13024-021-00442-7. Mol Neurodegener. 2021. PMID: 33853653 Free PMC article. - AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer.
Delettre C, Yuste VJ, Moubarak RS, Bras M, Lesbordes-Brion JC, Petres S, Bellalou J, Susin SA. Delettre C, et al. J Biol Chem. 2006 Mar 10;281(10):6413-27. doi: 10.1074/jbc.M509884200. Epub 2005 Dec 19. J Biol Chem. 2006. PMID: 16365034 - Life with or without AIF.
Hangen E, Blomgren K, Bénit P, Kroemer G, Modjtahedi N. Hangen E, et al. Trends Biochem Sci. 2010 May;35(5):278-87. doi: 10.1016/j.tibs.2009.12.008. Epub 2010 Feb 6. Trends Biochem Sci. 2010. PMID: 20138767 Review. - Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2).
Elguindy MM, Nakamaru-Ogiso E. Elguindy MM, et al. J Biol Chem. 2015 Aug 21;290(34):20815-20826. doi: 10.1074/jbc.M115.641498. Epub 2015 Jun 10. J Biol Chem. 2015. PMID: 26063804 Free PMC article. - Role of apoptosis-inducing factor (Aif) in the T cell lineage.
Prabhu SB, Khalsa JK, Banerjee H, Das A, Srivastava S, Mattoo HR, Thyagarajan K, Tanwar S, Das DS, Majumdar SS, George A, Bal V, Durdik JM, Rath S. Prabhu SB, et al. Indian J Med Res. 2013 Nov;138(5):577-90. Indian J Med Res. 2013. PMID: 24434313 Free PMC article. Review.
Cited by
- IsoFrog: a reversible jump Markov Chain Monte Carlo feature selection-based method for predicting isoform functions.
Liu Y, Yang C, Li HD, Wang J. Liu Y, et al. Bioinformatics. 2023 Sep 2;39(9):btad530. doi: 10.1093/bioinformatics/btad530. Bioinformatics. 2023. PMID: 37647643 Free PMC article. - Apoptosis-inducing factor: a mitochondrial protein associated with metabolic diseases-a narrative review.
Zong L, Liang Z. Zong L, et al. Cardiovasc Diagn Ther. 2023 Jun 30;13(3):609-622. doi: 10.21037/cdt-23-123. Epub 2023 Jun 19. Cardiovasc Diagn Ther. 2023. PMID: 37405018 Free PMC article. Review. - AIF3 splicing switch triggers neurodegeneration.
Liu S, Zhou M, Ruan Z, Wang Y, Chang C, Sasaki M, Rajaram V, Lemoff A, Nambiar K, Wang JE, Hatanpaa KJ, Luo W, Dawson TM, Dawson VL, Wang Y. Liu S, et al. Mol Neurodegener. 2021 Apr 14;16(1):25. doi: 10.1186/s13024-021-00442-7. Mol Neurodegener. 2021. PMID: 33853653 Free PMC article. - Alopecia in Harlequin mutant mice is associated with reduced AIF protein levels and expression of retroviral elements.
Hintze M, Griesing S, Michels M, Blanck B, Wischhof L, Hartmann D, Bano D, Franz T. Hintze M, et al. Mamm Genome. 2021 Feb;32(1):12-29. doi: 10.1007/s00335-020-09854-0. Epub 2020 Dec 26. Mamm Genome. 2021. PMID: 33367954 Free PMC article. - Role of apoptosis-inducing factor in perinatal hypoxic-ischemic brain injury.
Rodriguez J, Li T, Xu Y, Sun Y, Zhu C. Rodriguez J, et al. Neural Regen Res. 2021 Feb;16(2):205-213. doi: 10.4103/1673-5374.290875. Neural Regen Res. 2021. PMID: 32859765 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases