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

Tools

Item Type:	Article
Title:	MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria
Creators Name:	Zaltsman, Y., Shachnai, L., Yivgi-Ohana, N., Schwarz, M., Maryanovich, M., Houtkooper, R.H., Vaz, F.M., De Leonardis, F., Fiermonte, G., Palmieri, F., Gillissen, B., Daniel, P.T., Jimenez, E., Walsh, S., Koehler, C.M., Roy, S.S., Walter, L., 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
ISSN:	1465-7392
Publisher:	Nature Publishing Group
Volume:	12
Number:	6
Page Range:	553-562
Date:	June 2010
Official Publication:	https://doi.org/10.1038/ncb2057
PubMed:	View item in PubMed

Repository Staff Only: item control page