Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 21, Pages 8738-8743Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1212976110
Keywords
transcriptional regulation; mitochondria; oxidative metabolism; metabolic reprogramming; muscle plasticity
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Funding
- Swiss National Science Foundation [SNF PP00A-110746]
- Muscular Dystrophy Association
- SwissLife Jubilaumsstiftung fur Volksgesundheit und Medizinische Forschung
- Swiss Society for Research on Muscle Diseases
- Swiss Diabetes Association
- Roche Research Foundation
- United Mitochondrial Disease Foundation
- Association Francaise Contre les Myopathies
- University of Basel
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The peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) controls metabolic adaptations. We now show that PGC-1 alpha in skeletal muscle drives the expression of lactate dehydrogenase (LDH) B in an estrogen-related receptor-alpha-dependent manner. Concomitantly, PGC-1 alpha reduces the expression of LDH A and one of its regulators, the transcription factor myelocytomatosis oncogene. PGC-1 alpha thereby coordinately alters the composition of the LDH complex and prevents the increase in blood lactate during exercise. Our results show how PGC-1 alpha actively coordinates lactate homeostasis and provide a unique molecular explanation for PGC-1 alpha-mediated muscle adaptations to training that ultimately enhance exercise performance and improve metabolic health.
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