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Wuest 2018 Cell Metab

From Bioblast
Publications in the MiPMap
Wüst S, Dröse S, Heidler J, Wittig I, Klockner I, Franko A, Bonke E, Günther S, Gärtner U, Boettger T, Braun T (2018) Metabolic maturation during muscle stem cell differentiation is achieved by miR-1/133a-mediated inhibition of the Dlk1-Dio3 mega gene cluster. Cell Metab 27:1026-39.

» PMID: 29606596

Wuest S, Droese S, Heidler J, Wittig I, Klockner I, Franko A, Bonke E, Guenther S, Gaertner U, Boettger T, Braun T (2018) Cell Metab

Abstract: Muscle stem cells undergo a dramatic metabolic switch to oxidative phosphorylation during differentiation, which is achieved by massively increased mitochondrial activity. Since expression of the muscle-specific miR-1/133a gene cluster correlates with increased mitochondrial activity during muscle stem cell (MuSC) differentiation, we examined the potential role of miR-1/133a in metabolic maturation of skeletal muscles in mice. We found that miR-1/133a downregulate Mef2A in differentiated myocytes, thereby suppressing the Dlk1-Dio3 gene cluster, which encodes multiple microRNAs inhibiting expression of mitochondrial genes. Loss of miR-1/133a in skeletal muscles or increased Mef2A expression causes continuous high-level expression of the Dlk1-Dio3 gene cluster, compromising mitochondrial function. Failure to terminate the stem cell-like metabolic program characterized by high-level Dlk1-Dio3 gene cluster expression initiates profound changes in muscle physiology, essentially abrogating endurance running. Our results suggest a major role of miR-1/133a in metabolic maturation of skeletal muscles but exclude major functions in muscle development and MuSC maintenance. Keywords: Dlk1-Dio3, Mef2A, miR-1, miR-133a, microRNA, Skeletal muscle metabolism, Skeletal muscle mitochondria, Skeletal muscle stem cells Bioblast editor: Kandolf G O2k-Network Lab: DE Frankfurt Droese S

Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, Exercise physiology;nutrition;life style 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Intact cells 

Coupling state: OXPHOS  Pathway: N, S, CIV  HRR: Oxygraph-2k 

Labels, 2018-05