Crosstalk between Drp1 phosphorylation sites during mitochondrial remodeling and their impact on metabolic adaptation.
Drp1
brown adipose tissue
insulin resistance
metabolic syndrome
mitochondrial dynamics
mitochondrial respiration
phosphorylation
thermoneutrality
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
24 08 2021
24 08 2021
Historique:
received:
14
09
2020
revised:
07
06
2021
accepted:
29
07
2021
entrez:
25
8
2021
pubmed:
26
8
2021
medline:
12
2
2022
Statut:
ppublish
Résumé
Mitochondria constantly undergo fusion and fission events, referred as mitochondrial dynamics, which determine mitochondrial architecture and bioenergetics. Cultured cell studies demonstrate that mitochondrial dynamics are acutely regulated by phosphorylation of the mitochondrial fission orchestrator dynamin-related protein 1 (Drp1) at S579 or S600. However, the physiological impact and crosstalk of these phosphorylation sites is poorly understood. Here, we describe the functional interrelation between S579 and S600 phosphorylation sites in vivo and their role on mitochondrial remodeling. Mice carrying a homozygous Drp1 S600A knockin (Drp1 KI) mutation display larger mitochondria and enhanced lipid oxidation and respiratory capacities, granting improved glucose tolerance and thermogenic response upon high-fat feeding. Housing mice at thermoneutrality blunts these differences, suggesting a role for the brown adipose tissue in the protection of Drp1 KI mice against metabolic damage. Overall, we demonstrate crosstalk between Drp1 phosphorylation sites and provide evidence that their modulation could be used in the treatment and prevention of metabolic diseases.
Identifiants
pubmed: 34433037
pii: S2211-1247(21)00999-2
doi: 10.1016/j.celrep.2021.109565
pmc: PMC8411118
pii:
doi:
Substances chimiques
Dnm1l protein, mouse
EC 3.6.5.5
Dynamins
EC 3.6.5.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109565Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.V.-A., M.J., J.L.S.-G., A.C., A.V., L.D., A.N.G., and C.C. are employees of Nestlé Research Ltd., Société des Produits Nestlé SA. A.G.L. is co-founder and CSO of Eisbach Bio GmbH.
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