title: MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria.
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.
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Zaltsman
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Shachnai
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Yivgi-Ohana
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Maria
authors.initials: M
authors.lastname: Maryanovich
authors.affiliation: Laboratory for Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Riekelt H
authors.initials: RH
authors.lastname: Houtkooper
authors.affiliation: Department of Clinical Chemistry and Pediatrics, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
authors.forename: Frédéric Maxime
authors.initials: FM
authors.lastname: Vaz
authors.affiliation: Department of Pharmaco-Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Leonardis
authors.affiliation: Department of Pharmaco-Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fiermonte
authors.affiliation: Department of Pharmaco-Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Palmieri
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, University Medical Center Charité, Humboldt University, 13125 Berlin, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gillissen
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, University Medical Center Charité, Humboldt University, 13125 Berlin, Germany.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Daniel
authors.affiliation: Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Jimenez
authors.affiliation: Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Walsh
authors.affiliation: Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Koehler
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Soumya Sinha
authors.initials: SS
authors.lastname: Roy
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Walter
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: György
authors.initials: G
authors.lastname: Hajnóczky
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Atan
authors.initials: A
authors.lastname: Gross
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D053218:Receptors, Death Domain / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C550380:Mtch2 protein, mouse; D053218:Receptors, Death Domain