Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release
Year: 2017
Type: article
Abstract: Significance This paper describes the finding that mitochondria synthesize and release melatonin and have their selective G protein-coupled receptor (GPCR) in the outer membrane. We further demonstrate that mitochondrial melatonin type 1 receptors respond to melatonin by activating heterotrimeric G proteins located in the intermembrane space and inhibit stress-mediated cytochrome c release. This remarkable insight changes our classical understanding of biological GPCR function by showing that a cellular organelle both synthesizes and has a signaling receptor for a specific ligand. Implicit with our original work is the existence of an automitocrine signaling pathway by which melatonin prevents neurodegeneration associated with mitochondrial cytochrome c release and downstream caspase activation.
Authors: Yalikun Suofu, Wei Li, Frédéric G. Jean-Alphonse, Jiaoying Jia, Nicolas K. Khattar, Jiatong Li, Sergei V. Baranov, Daniela Leronni, Amanda C. Mihalik, Yanqing He, Erika Cecon, Vanessa L. Wehbi, JinHo Kim, Brianna E. Heath, Oxana V. Baranova, Xiaomin Wang, Matthew J. Gable, Eric S. Kretz, Giulietta Di Benedetto, Timothy R. Lezon, Lisa M. Ferrando, Timothy M. Larkin, Mara Sullivan, Svitlana Yablonska, Jingjing Wang, M. Beth Minnigh, Gérald Guillaumet, Franck Suzenet, R. Mark Richardson, Samuel M. Poloyac, Donna B. Stolz, Ralf Jockers, Paula A. Witt-Enderby, Diane L. Carlisle, Jean-Pierre Vilardaga, Robert M. Friedlander
Institutions: University of Pittsburgh, Tsinghua University, Central South University, Second Xiangya Hospital of Central South University, Centre National de la Recherche Scientifique, Inserm, Institut Cochin, Université Paris Descartes, National Research Council, Université d'Orléans, Institut de Chimie Organique et Analytique, Duquesne University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, National Institutes of Health, Institut national des sciences de l'Univers, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: G1535738422, G1969149739, G29348844, Determinants de l'Identité : de la molécule à l'individu, G3851708603, G4750690843, G568493576, G6072372228, G6889604184, Synthèse Organique : des molécules au vivant, Université Sorbonne Paris Cité, Development of innovative drugs targeting G protein-coupled receptor heteromers, G9000037463, G9000041113, G9000044477, G9000091847
OpenAlex ID: W2750856430