Zaltsman, YehuditShachnai, LiatYivgi-Ohana, NatalieSchwarz, MichalMaryanovich, MariaHoutkooper, Riekelt H.Vaz, Frederic MaximeDe Leonardis, FrancescoFiermonte, GiuseppePalmieri, FerdinandoGillissen, BernhardDaniel, Peter T.Jimenez, ErinWalsh, SusanKoehler, Carla M.Roy, Soumya SinhaWalter, LudivineHajnoczky, GyoergyGross, Atan2011-12-162011-12-162011-12-16201010.1038/ncb2057https://infoscience.epfl.ch/handle/20.500.14299/75467WOS:000278213400007The BH3-only BID (BH3-interacting domain death agonist) protein 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.Outer-MembraneCell-DeathCre RecombinaseBcl-2 FamilyInduce ApoptosisBarth-SyndromeBaxProteinsPermeabilizationOligomerizationtext::journal::journal article::research article