Author, as appears in the article.: Valera-Alberni, Miriam; Joffraud, Magali; Miro-Blanch, Joan; Capellades, Jordi; Junza, Alexandra; Dayon, Loic; Galindo, Antonio Nunez; Sanchez-Garcia, Jose L; Valsesia, Armand; Cercillieux, Angelique; Soellner, Flavia; Ladurner, Andreas G; Yanes, Oscar; Canto, Carles
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Junza Martínez, Alexandra / Miró Blanch, Joan / Yanes Torrado, Óscar
Keywords: Thermoneutrality Phosphorylation Pathway Morphology Mitochondrial respiration Mitochondrial dynamics Metabolic syndrome Liver protects Kinase Insulin-resistance Insulin resistance Fission factor Dynamin-related protein-1 Drp1 Degradation Deficiency Brown adipose tissue Adipocytes
Abstract: 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.
Thematic Areas: Medicina ii Medicina i General medicine General biochemistry,genetics and molecular biology Engenharias iv Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all)
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: oscar.yanes@urv.cat alexandra.junza@urv.cat joan.miro@estudiants.urv.cat
Author identifier: 0000-0003-3695-7157 0000-0001-7205-0419 0000-0003-3179-0554
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Cell Reports. 36 (8): 109565-
APA: Valera-Alberni, Miriam; Joffraud, Magali; Miro-Blanch, Joan; Capellades, Jordi; Junza, Alexandra; Dayon, Loic; Galindo, Antonio Nunez; Sanchez-Garcia, (2021). Crosstalk between Drp1 phosphorylation sites during mitochondrial remodeling and their impact on metabolic adaptation. Cell Reports, 36(8), 109565-. DOI: 10.1016/j.celrep.2021.109565
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV