MyoD Regulates Skeletal Muscle Oxidative Metabolism Cooperatively with Alternative NF-κB
Autor: | Denis C. Guttridge, Katherine J. Ladner, Kambiz Mousavi, Ruoning Wang, Jonathan Shintaku, Jin-Mo Gu, Erin E. Talbert, Jennifer M. Peterson, Dustin R. Williams, Vittorio Sartorelli |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
mitochondrial biogenesis RelB Muscle Development MyoD ppargc1b Article General Biochemistry Genetics and Molecular Biology Myoblasts Mice 03 medical and health sciences MyoD Protein oxidative metabolism medicine Animals Myocyte NF-kappaB skeletal muscle Muscle Skeletal lcsh:QH301-705.5 Myogenin PGC-1beta PITX2 Myogenesis Chemistry Transcription Factor RelB NF-kappa B Skeletal muscle musculoskeletal system Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mitochondria 030104 developmental biology medicine.anatomical_structure Mitochondrial biogenesis Biochemistry lcsh:Biology (General) Oxidation-Reduction Muscle Contraction Protein Binding Signal Transduction |
Zdroj: | Cell Reports, Vol 17, Iss 2, Pp 514-526 (2016) |
ISSN: | 2211-1247 |
Popis: | SummaryMyoD is a key regulator of skeletal myogenesis that directs contractile protein synthesis, but whether this transcription factor also regulates skeletal muscle metabolism has not been explored. In a genome-wide ChIP-seq analysis of skeletal muscle cells, we unexpectedly observed that MyoD directly binds to numerous metabolic genes, including those associated with mitochondrial biogenesis, fatty acid oxidation, and the electron transport chain. Results in cultured cells and adult skeletal muscle confirmed that MyoD regulates oxidative metabolism through multiple transcriptional targets, including PGC-1β, a master regulator of mitochondrial biogenesis. We find that PGC-1β expression is cooperatively regulated by MyoD and the alternative NF-κB signaling pathway. Bioinformatics evidence suggests that this cooperativity between MyoD and NF-κB extends to other metabolic genes as well. Together, these data identify MyoD as a regulator of the metabolic capacity of mature skeletal muscle to ensure that sufficient energy is available to support muscle contraction. |
Databáze: | OpenAIRE |
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