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

Item Type:Article
Title:MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria
Creators Name:Zaltsman, Y. and Shachnai, L. and Yivgi-Ohana, N. and Schwarz, M. and Maryanovich, M. and Houtkooper, R.H. and Vaz, F.M. and De Leonardis, F. and Fiermonte, G. and Palmieri, F. and Gillissen, B. and Daniel, P.T. and Jimenez, E. and Walsh, S. and Koehler, C.M. and Roy, S.S. and Walter, L. and Hajnoczky, G. and Gross, A.
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.
Keywords:Apoptosis, BH3 Interacting Domain Death Agonist Protein, Death Domain Receptors, Fibroblasts, Liver Mitochondria, Membrane Transport Proteins, Mitochondria, Mitochondrial Membranes, Mitochondrial Proteins, Animals, Mice
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:553-562
Date:June 2010
Official Publication:https://doi.org/10.1038/ncb2057
PubMed:View item in PubMed

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