Mitochondrial fatty acid oxidation is stimulated by red light irradiation.

Keratinocytes are the primary constituents of sunlight-exposed epidermis. In these cells, ultraviolet (UV) A light completely inhibited oxidative phosphorylation, while equivalent doses of blue and green light preserved metabolic fluxes but reduced viability. In contrast, red light enhanced proliferation and elevated basal and maximal oxygen consumption rates for 48 h without altering protein levels of the electron transport chain. Targeted flux analysis revealed that red light specifically activates AMP-activating protein kinase (AMPK)-dependent mitochondrial fatty acid oxidation. This was accompanied by reduced levels of free fatty acids and increased acetyl-CoA carboxylase phosphorylation. Together, our results characterize wavelength-selective regulation of keratinocyte metabolism: UV/visible wavelengths induce damage, while red light triggers AMPK-dependent fatty acid oxidation, providing a mechanistic explanation for photobiomodulation in epidermal cells. Impact statement Sunlight impacts skin cells in surprising ways. While UVA harms energy production and blue/green light reduces survival, red light boosts keratinocyte metabolism. We show that red light activates AMPK-dependent fatty acid oxidation, enhancing proliferation and energy use. These findings reveal how specific wavelengths can damage or stimulate skin cells.