دورية أكاديمية
أعرض في EDS

The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions.

التفاصيل البيبلوغرافية
العنوان: The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions.
المؤلفون: Fasciani I; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Petragnano F; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Wang Z; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Edwards R; Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom., Telugu N; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Pietrantoni I; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Zabel U; Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany., Zauber H; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Grieben M; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Terzenidou ME; Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom., Di Gregorio J; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Pellegrini C; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Santini S Jr; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy., Taddei AR; Section of Electron Microscopy, Great Equipment Center, University of Tuscia, Viterbo, Italy., Pohl B; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Aringhieri S; Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy., Carli M; Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy., Aloisi G; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Marampon F; Department of Radiotherapy, University of Roma La Sapienza, Roma, Italy., Charlesworth E; School of Physics and Astronomy, University of St Andrews, St Andrews, United Kingdom., Roman A; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Diecke S; Max Delbrück Center for Molecular Medicine, Berlin, Germany., Flati V; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Giorgi F; Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy., Amicarelli F; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy., Tobin AB; Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom., Scarselli M; Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy., Tokatlidis K; Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom., Rossi M; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Lohse MJ; Max Delbrück Center for Molecular Medicine, Berlin, Germany.; Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.; ISAR Bioscience Institute, Munich, Germany., Annibale P; Max Delbrück Center for Molecular Medicine, Berlin, Germany.; School of Physics and Astronomy, University of St Andrews, St Andrews, United Kingdom., Maggio R; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
المصدر: PLoS biology [PLoS Biol] 2024 Apr 29; Vol. 22 (4), pp. e3002582. Date of Electronic Publication: 2024 Apr 29 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, [2003]-
مواضيع طبية MeSH: Cell Respiration* , Mitochondria*/metabolism , Receptor, Muscarinic M2*/metabolism , Receptor, Muscarinic M2*/genetics, Animals ; Humans ; Mice ; Cell Proliferation ; HEK293 Cells ; Induced Pluripotent Stem Cells/metabolism ; Oxidative Phosphorylation ; Oxygen Consumption ; Reactive Oxygen Species/metabolism ; Stress, Physiological
مستخلص: 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. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human-induced pluripotent stem cells (hiPSCs), reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signaling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism that cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Fasciani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: 0 (Reactive Oxygen Species)
0 (Receptor, Muscarinic M2)
0 (CHRM2 protein, human)
تواريخ الأحداث: Date Created: 20240429 Date Completed: 20240514 Latest Revision: 20240603
رمز التحديث: 20240604
مُعرف محوري في PubMed: PMC11093360
DOI: 10.1371/journal.pbio.3002582
PMID: 38683874
قاعدة البيانات: MEDLINE
الوصف
تدمد:1545-7885
DOI:10.1371/journal.pbio.3002582