title: Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A.
abstract: The peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) controls metabolic adaptations. We now show that PGC-1α in skeletal muscle drives the expression of lactate dehydrogenase (LDH) B in an estrogen-related receptor-α-dependent manner. Concomitantly, PGC-1α reduces the expression of LDH A and one of its regulators, the transcription factor myelocytomatosis oncogene. PGC-1α thereby coordinately alters the composition of the LDH complex and prevents the increase in blood lactate during exercise. Our results show how PGC-1α actively coordinates lactate homeostasis and provide a unique molecular explanation for PGC-1α-mediated muscle adaptations to training that ultimately enhance exercise performance and improve metabolic health.
authors: Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
authors: Serge
authors: S
authors: Summermatter
authors: Gesa
authors: G
authors: Santos
authors: Joaquín
authors: J
authors: Pérez-Schindler
authors: Christoph
authors: C
authors: Handschin
mesh_terms: D000818:Animals; D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D047628:Estrogen Receptor alpha; D007527:Isoenzymes; D009124:Muscle Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C409667:lactate dehydrogenase 1
keywords: metabolic reprogramming; mitochondria; muscle plasticity; oxidative metabolism; transcriptional regulation
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