Irene Fasciani, Francesco Petragnano, Ziming Wang, Ruairidh Edwards, Narasimha Telugu, Ilaria Pietrantoni, Ulrike Zabel, Henrik Zauber, Marlies Grieben, Maria E Terzenidou, Jacopo Di Gregorio, Cristina Pellegrini, Silvano Santini, Anna R Taddei, Bärbel Pohl, Stefano Aringhieri, Marco Carli, Gabriella Aloisi, Francesco Marampon, Eve Charlesworth, Alexandra Roman, Sebastian Diecke, Vincenzo Flati, Franco Giorgi, Fernanda Amicarelli, Andrew B Tobin, Marco Scarselli, Kostas Tokatlidis, Mario Rossi, Martin J Lohse, Paolo Annibale, Roberto Maggio
Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation...
April 29, 2024: PLoS Biology