In gratitude of the loyal support of our members, the CNS is offering complimentary 2021 Annual Meeting registration to all members! Learn more.

  • Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release and modulation of cerebral ischemic injury

    Final Number:
    4167

    Authors:
    Yalikun Suofu; Wei Li; Jean-Pierre Vilardaga; Robert Max Friedlander MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2017 Annual Meeting - Late Breaking Science

    Introduction: G-protein coupled receptors (GPCRs) are classically characterized as cell surface receptors transmitting extracellular signals into cells.

    Methods: Mitochondrial purification and evaluation, MCAO

    Results: Here we show that central components of a GPCR signaling system constituted of the melatonin type 1 receptor (MT1), its associated G protein, and ß-arrestins are on and within neuronal mitochondria. We discovered that the ligand, melatonin, is exclusively synthetized in the mitochondrial matrix and activates the mitochondrial MT1 signal transduction pathway inhibiting stress mediated cytochrome c release and caspase activation. These findings coupled to our observation that mitochondrial MT1 overexpression reduces ischemic brain injury in mice delineate a novel mitochondrial GPCR mechanism contributing to the neuroprotective action of melatonin.

    Conclusions: 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, with particular importance to both the ageing process of well as acute (i.e. cerebral ischemia, TBI) and chronic (i.e. ALS, Huntington’s disease) neurodegenerative diseases.

    Patient Care: Understanding mitochondrial melatonin physiology may allow for the development of novel neuroprotective strategies.

    Learning Objectives: Understand mechanisms of endogenous melatonin-mediated protection

    References: PNAS In Press (Publication week of September 4)

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy