Skeletal Muscle PGC-1α Controls Whole-body Lactate Homeostasis Through Estrogen-related Receptor α-dependent Activation of LDH B and Repression of LDH A

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 May 8

PMID 23650363

Citations 71

Authors

Serge Summermatter

Gesa Santos

Joaquin Perez-Schindler

Christoph Handschin

Affiliations

Soon will be listed here.

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.

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