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

Yehudit Zaltsman, Liat Shachnai, Natalie Yivgi-Ohana, Michal Schwarz, Maria Maryanovich, Riekelt H. Houtkooper, Frédéric Maxime Vaz, Francesco De Leonardis, Giuseppe Fiermonte, Ferdinando Palmieri, Bernhard Gillissen, Peter T. Daniel, Erin Jimenez, Susan Walsh, Carla M. Koehler, Soumya Sinha Roy, Ludivine Walter, György Hajnóczky, Atan Gross

Research output: Contribution to journalArticle

109 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalNature Cell Biology
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    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., Hajnóczky, G., & Gross, A. (2010). MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria. Nature Cell Biology, 12(6), 553-562. https://doi.org/10.1038/ncb2057