Details

Autor(en) / Beteiligte

• Suofu, Yalikun
• Li, Wei
• Jean-Alphonse, Frédéric G.
• Jia, Jiaoying
• Khattar, Nicolas K.
• Li, Jiatong
• Baranov, Sergei V.
• Leronni, Daniela
• Mihalik, Amanda C.
• He, Yanqing
• Cecon, Erika
• Wehbi, Vanessa L.
• Kim, JinHo
• Heath, Brianna E.
• Baranova, Oxana V.
• Wang, Xiaomin
• Gable, Matthew J.
• Kretz, Eric S.
• Di Benedetto, Giulietta
• Lezon, Timothy R.
• Ferrando, Lisa M.
• Larkin, Timothy M.
• Sullivan, Mara
• Yablonska, Svitlana
• Wang, Jingjing
• Minnigh, M. Beth
• Guillaumet, Gérald
• Suzenet, Franck
• Richardson, R. Mark
• Poloyac, Samuel M.
• Stolz, Donna B.
• Jockers, Ralf
• Witt-Enderby, Paula A.
• Carlisle, Diane L.
• Vilardaga, Jean-Pierre
• Friedlander, Robert M.

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2017-09, Vol.114 (38), p.E7997-E8006

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT₁), its associated G protein, and β-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT₁ signal-transduction pathway inhibiting stress-mediated cytochrome c release and caspase activation. These findings coupled with our observation that mitochondrial MT₁ overexpression reduces ischemic brain injury in mice delineate a mitochondrial GPCR mechanism contributing to the neuroprotective action of melatonin. We propose a new term, “automitocrine,” analogous to “autocrine” when a similar phenomenon occurs at the cellular level, to describe this unexpected intracellular organelle ligand–receptor pathway that opens a new research avenue investigating mitochondrial GPCR biology.