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Nat Cell Biol. 2010 Jun;12(6):553-562. doi: 10.1038/ncb2057. Epub 2010 May 2.

MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria.

Author information

1
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
2
Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
3
Department of Clinical Chemistry and Pediatrics, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
4
Department of Pharmaco-Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
5
Department of Hematology, Oncology, and Tumor Immunology, University Medical Center Charité, Humboldt University, 13125 Berlin, Germany.
6
Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095, USA.
7
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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Contributed equally

Abstract

The BH3-only BID protein (BH3-interacting domain death agonist) has a critical function in the death-receptor pathway in the liver by triggering mitochondrial outer membrane permeabilization (MOMP). Here we show that MTCH2/MIMP (mitochondrial carrier homologue 2/Met-induced mitochondrial protein), a novel truncated BID (tBID)-interacting protein, is a surface-exposed outer mitochondrial membrane protein that facilitates the recruitment of tBID to mitochondria. Knockout of MTCH2/MIMP in embryonic stem cells and in mouse embryonic fibroblasts hinders the recruitment of tBID to mitochondria, the activation of Bax/Bak, MOMP, and apoptosis. Moreover, conditional knockout of MTCH2/MIMP in the liver decreases the sensitivity of mice to Fas-induced hepatocellular apoptosis and prevents the recruitment of tBID to liver mitochondria both in vivo and in vitro. In contrast, MTCH2/MIMP deletion had no effect on apoptosis induced by other pro-apoptotic Bcl-2 family members and no detectable effect on the outer membrane lipid composition. These loss-of-function models indicate that MTCH2/MIMP has a critical function in liver apoptosis by regulating the recruitment of tBID to mitochondria.

PMID:
20436477
PMCID:
PMC4070879
DOI:
10.1038/ncb2057
[Indexed for MEDLINE]
Free PMC Article
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