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Mitochondria-targeted melatonin photorelease supports the presence of melatonin MT1 receptors in mitochondria inhibiting respiration
PAGANO ZOTTOLA, Antonio
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
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Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
PAGANO ZOTTOLA, Antonio
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
CANNICH, Astrid
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MUÑOZ, Lourdes
Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia [MCS (IQAC-CSIC)]
Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia [MCS (IQAC-CSIC)]
SERRA, Carme
Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia [MCS (IQAC-CSIC)]
Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia [MCS (IQAC-CSIC)]
MARSICANO, Giovanni
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
BELLOCCHIO, Luigi
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
LLEBARIA, Amadeu
Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia [MCS (IQAC-CSIC)]
< Reduce
Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia [MCS (IQAC-CSIC)]
Language
EN
Article de revue
This item was published in
Cell Chemical Biology. 2023-08-17, vol. 30, n° 8, p. 920-932
English Abstract
The presence of signaling-competent G protein-coupled receptors in intracellular compartments is increasinglyrecognized. Recently, the presence of Gi/o protein-coupled melatonin MT1 receptors in mitochondriahas been revealed, ...Read more >
The presence of signaling-competent G protein-coupled receptors in intracellular compartments is increasinglyrecognized. Recently, the presence of Gi/o protein-coupled melatonin MT1 receptors in mitochondriahas been revealed, in addition to the plasma membrane. Melatonin is highly cell permeant, activating plasmamembrane and mitochondrial receptors equally. Here, we present MCS-1145, a melatonin derivative bearinga triphenylphosphonium cation for specific mitochondrial targeting and a photocleavable o-nitrobenzylgroup releasing melatonin upon illumination. MCS-1145 displayed low affinity for MT1 and MT2 but spontaneouslyaccumulated in mitochondria, where it was resistant to washout. Uncaged MCS-1145 and exogenousmelatonin recruited b-arrestin 2 toMT1 in mitochondria and inhibited oxygen consumption inmitochondriaisolated from HEK293 cells only when expressing MT1 and from mouse cerebellum of WT mice but notfrom MT1-knockout mice. Overall, we developed the first mitochondria-targeted photoactivatable melatoninligand and demonstrate that melatonin inhibits mitochondrial respiration through mitochondrial MT1receptors.Read less <
English Keywords
Melatonin
Melatonin receptors
Mitochondria-targeted caged melatonin ligand
Photopharmacology
Mitochondrial respiration
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