Liang 2016 J Biol Chem

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Liang X, Liu J, Zhou D, Lai L, Xiao L, Liu L, Fu T, Kong Y, Zhou Q, Vega RB, Zhu MS, Kelly DP, Gao X, Gan Z (2016) Exercise inducible lactate dehydrogenase B regulates mitochondrial function in skeletal muscle. J Biol Chem 291:25306-18

» PMID: 27738103

Liang X, Liu J, Zhou D, Lai L, Xiao L, Liu L, Fu T, Kong Y, Zhou Q, Vega RB, Zhu MS, Kelly DP, Gao X, Gan Z (2016) J Biol Chem

Abstract: Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate, which are critical fuel metabolites of skeletal muscle particularly during exercise. However, the physiological relevance of LDH remains poorly understood. Here we show that Ldhb expression is induced by exercise in human muscle and negatively correlated with changes in intramuscular pH levels, a marker of lactate production, during isometric exercise. We found that the expression of Ldhb is regulated by exercise-induced peroxisome proliferator-activated receptor-g coactivator 1α (PGC-1α). Ldhb gene promoter reporter studies demonstrated that PGC-1α activates Ldhb gene expression through multiple conserved estrogen-related receptor (ERR) and myocyte enhancer factor 2 (MEF2) binding sites. Transgenic mice overexpressing Ldhb in muscle (muscle creatine kinase [MCK]-Ldhb) exhibited increased exercise performance and enhanced oxygen consumption during exercise. MCK-Ldhb muscle was shown to have enhanced mitochondrial enzyme activity and increased mitochondrial gene expression, suggesting an adaptive oxidative muscle transformation. In addition, mitochondrial respiration capacity was increased and lactate production decreased in MCK-Ldhb skeletal myotubes in culture. Together, these results identified a previously unrecognized Ldhb-driven alteration in muscle mitochondrial function and suggested a mechanism for the adaptive metabolic response induced by exercise training.

Copyright © 2016, The American Society for Biochemistry and Molecular Biology.

Keywords: Bioenergetics, Exercise, Gene regulation, Mitochondria, Skeletal muscle Bioblast editor: Kandolf G O2k-Network Lab: CN Nanjing Gan Z


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k