Mitochondrial Fatty Acid Oxidation is Stimulated by Red Light Irradiation

The skin is our largest organ, and also the most exposed to solar radiation. As mitochondria within skin cells are rich in endophotosensitizers such as NADH, FADH 2 , and cytochromes, we studied the effects of different UV and visible light wavelengths on metabolic fluxes in keratinocytes, the main cell type in the epidermis. We find that 36 J/cm 2 of UV light (λ max at 365 nm) leads to a complete inhibition of oxidative phosphorylation. The same light dose at other wavelengths (blue light, 450 nm, and green light, 517 nm) did not affect metabolic fluxes, but reduced cell viability, probably by photosensitizing oxidation. Strikingly, red light (660 nm) not only did not decrease cell viability, but also enhanced cell proliferation as well as basal and maximal oxygen consumption rates for up to two days after irradiation. To uncover the mechanisms in which this unexpected long-lived metabolic enhancement occurred, we measured quantities of oxidative phosphorylation-related proteins and oxygen consumption in permeabilized cells, which were unchanged. This result is indicative of a modulation of cytosolic metabolic processes by red light. Subsequently, we measured glycolytic, glutamine-dependent, and fatty-acid supported metabolic fluxes and determined that red light specifically activates fatty acid oxidation by mitochondria. Overall, our results demonstrate that light modulates oxidative phosphorylation with different effects at distinct wavelengths. Interestingly, we uncover a novel and highly specific effect of red light modulating fatty acid oxidation in keratinocytes, providing a novel mechanistic explanation for the metabolic effects of photobiomodulation. Highlights Different UV and visible light wavelengths affect keratinocytes distinctly: UV leads to cell death and metabolic flux inhibition, while green light decreases viability without affecting oxygen consumption. Surprisingly, red light increases intact cell oxygen consumption up to two days post exposure. Red light exposure does not change the quantity or activity of components of oxidative phosphorylation in mitochondria. Increased mitochondrial respiration and ATP synthesis promoted by red light is fueled by enhanced fatty acid oxidation.