Wuest 2018 Cell Metab
|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.|
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