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Updated: Jul 16, 2026

Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
Published on: February 24, 2026
Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis
Takeshi Hashimoto1, Rajaa Hussien, Saji Oommen
1Department of Integrative Biology, University of California, Berkeley, CA 94720-3140 USA.
Abstract:
We hypothesized that in addition to serving as a fuel source and gluconeogenic precursor, lactate anion (La-) is a signaling molecule. Therefore, we screened genome-wide responses of L6 cells to elevated (10 and 20 mM) sodium-La- added to buffered, high-glucose media. Lactate increased reactive oxygen species (ROS) production and up-regulated 673 genes, many known to be responsive to ROS and Ca2+. The induction of genes encoding for components of the mitochondrial lactate oxidation complex was confirmed by independent methods (PCR and EMSA). Specifically, lactate increased monocarboxylate transporter-1 (MCT1) mRNA and protein expression within 1 h and cytochrome c oxidase (COX) mRNA and protein expression in 6 h. Increases in COX coincided with increases in peroxisome proliferator activated-receptor gamma coactivator-1alpha (PGC1alpha) expression and the DNA binding activity of nuclear respiratory factor (NRF)-2. We conclude that the lactate signaling cascade involves ROS production and converges on transcription factors affecting mitochondrial biogenesis.
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