Valera-Alberni 2021 Cell Rep

From Bioblast
Publications in the MiPMap
Valera-Alberni M, Joffraud M, Miro-Blanch J, Capellades J, Junza A, Dayon L, NΓΊΓ±ez Galindo A, Sanchez-Garcia JL, Valsesia A, Cercillieux A, SΓΆllner F, Ladurner AG, Yanes O, CantΓ³ C (2021) Crosstalk between Drp1 phosphorylation sites during mitochondrial remodeling and their impact on metabolic adaptation. Cell Rep 36:109565.

Β» PMID: 34433037 Open Access

Valera-Alberni Miriam, Joffraud Magali, Miro-Blanch Joan, Capellades Jordi, Junza Alexandra, Dayon Loic, Nunez Galindo Antonio, Sanchez-Garcia Jose L, Valsesia Armand, Cercillieux Angelique, Soellner Flavia, Ladurner Andreas G, Yanes Oscar, Canto Carles (2021) Cell Rep

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. β€’ Keywords: Drp1, Brown adipose tissue, Insulin resistance, Metabolic syndrome, Mitochondrial dynamics, Mitochondrial respiration, Phosphorylation, Thermoneutrality β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CH Lausanne Canto C


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression 


Organism: Mouse  Tissue;cell: Liver, Fat  Preparation: Homogenate, Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2021-09 

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