Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release

著者: Yalikun Suofu, Wěi Li, Frédéric 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 Heath, Oxana V. Baranova, Xiaomin Wang, Matthew 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 - Proceedings of the National Academy of Sciences, PNAS 2017 被引用: 411

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.