Mitochondrial Fatty Acid Oxidation is Stimulated by Red Light Irradiation

Abstract

Keratinocytes are the primary constituents of sunlight-exposed epidermis. In these cells, UVA 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 AMPK-dependent mitochondrial fatty acid oxidation. This was accompanied by reduced the 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. HighlightsUVA (365 nm) abolishes oxidative phosphorylation, while blue/green light (450/517 nm) induce photosensitized toxicity, without metabolic disruption. Red light (660 nm) boosts keratinocyte proliferation and sustains elevated mitochondrial respiration for 48 h. Permeabilized cell electron transport remains unchanged, implicating cytosolic (not mitochondrial) regulation of fuel utilization. Red light activates AMPK and phosphorylates/inhibits acetyl CoA carboxylase (ACC). Photobiomodulation with red light occurs through AMPK/ACC-mediated lipid oxidation, not direct respiratory chain modulation.