Roles of lactate in lactate oxidation complex, mitochondrial biogenesis and cell signaling in cultured L6 skeletal muscle cells

Functional adaptations of muscle cells to exercise involve alterations in cell structure (1, 2), mitochondrial density and respiratory capacity (3-5), solute transport (6), and energy substrate partitioning (7). We are interested in defining the role of lactate as a metabolic signal that affects gene transcription. During contractions, muscle [lactate] can rise 1-2 orders of magnitude, and it has been postulated that lactate may serve as a pseudo-hormone because of its influence on cellular redox state by affecting the NAD(+)/NADH ratio (6). However molecular mechanisms that cause these metabolic effects of lactate were uncharacterized. We hypothesized that lactate anion (La-) is a signaling molecule whose actions affect the transcription of specific genes. Therefore, we screened genome-wide responses of L6 cells to elevated (10 and 20 mM) concentrations of sodium lactate in buffered, high-glucose containing media. Here we report on our efforts to describe the possible contribution of lactate to the transcription of genes known to be involved in the muscular adaptations to exercise stress (8).