TY - JOUR
T1 - MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria
AU - Zaltsman, Yehudit
AU - Shachnai, Liat
AU - Yivgi-Ohana, Natalie
AU - Schwarz, Michal
AU - Maryanovich, Maria
AU - Houtkooper, Riekelt H.
AU - Vaz, Frédéric Maxime
AU - De Leonardis, Francesco
AU - Fiermonte, Giuseppe
AU - Palmieri, Ferdinando
AU - Gillissen, Bernhard
AU - Daniel, Peter T.
AU - Jimenez, Erin
AU - Walsh, Susan
AU - Koehler, Carla M.
AU - Roy, Soumya Sinha
AU - Walter, Ludivine
AU - Hajnóczky, György
AU - Gross, Atan
N1 - Funding Information:
We are grateful to S. Jung for advice regarding the animal studies; A. Harmelin, R. Haffner, A. Maizenberg, G. Damari and T. Berkutzki for help with the animal and ES cell studies; H. van Lenthe and F. Stet for technical assistance with the phospholipid analysis; T. Langer (University of Cologne) for the TAT-Cre plasmid; T. S. Tanaka (University of Illinois at Urbana-Champaign) for DNA probes for Brachyury; D. Wallach (Weizmann Institute) for anti-Fas antibodies and Richard Marcellus (McGill University) for recombinant adenoviruses. This study was supported in part by the USA–Israel Binational Science Foundation, the Ministero dell’Università e della Ricerca, the Apulia Region, and the University of Bari. It was also supported by a grant of the Prinses Beatrix Fonds to F.M.V. and grants of the Barth Syndrome Foundation to W.K. and F.M.V. A.G. is the incumbent of the Armour Family Career Development Chair of cancer research. E.A.J. is funded by a National Institutes of Health (NIH) Minority Access to Research Careers U*STAR Scholarship, and S.W. is funded by a NIH National Research Service Award.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
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U2 - 10.1038/ncb2057
DO - 10.1038/ncb2057
M3 - Article
C2 - 20436477
AN - SCOPUS:77953121576
SN - 1465-7392
VL - 12
SP - 553
EP - 562
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 6
ER -