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Ian4 is required for mitochondrial integrity and T cell survival.

Authors: Pandarpurkar, M  Wilson-Fritch, L  Corvera, S  Markholst, H  Hornum, L  Greiner, DL  Mordes, JP  Rossini, AA  Bortell, R 
Citation: Pandarpurkar M, etal., Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10382-7. Epub 2003 Aug 20.
Pubmed: (View Article at PubMed) PMID:12930893
DOI: Full-text: DOI:10.1073/pnas.1832170100

Apoptosis is a regulated cell death program controlled by extrinsic and intrinsic signaling pathways. The intrinsic pathway involves stress signals that activate pro-apoptotic members of the Bcl-2 family, inducing permeabilization of mitochondria and release of apoptogenic factors. These proteins localize to the outer mitochondrial membrane. Ian4, a mitochondrial outer membrane protein with GTP-binding activity, is normally present in thymocytes, T cells, and B cells. We and others have recently discovered that a mutation in the rat Ian4 gene results in severe T cell lymphopenia that is associated with the expression of autoimmune diabetes. The mechanism by which Ian4 controls T cell homeostasis is unknown. Here we show that the absence of Ian4 in T cells causes mitochondrial dysfunction, increased mitochondrial levels of stress-inducible chaperonins and a leucine-rich protein, and T cell-specific spontaneous apoptosis. T cell activation and caspase 8 inhibition both prevented apoptosis, whereas transfection of T cells with Ian4-specific small interfering RNA recapitulated the apoptotic phenotype. The findings establish Ian4 as a tissue-specific regulator of mitochondrial integrity.

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CRRD Object Information
CRRD ID: 2303776
Created: 2009-02-26
Species: All species
Last Modified: 2009-02-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.