Mitochondrial Fatty Acid Oxidation is Stimulated by Red Light Irradiation
Posted on: 19 December 2025
Preprint posted on 23 June 2025
Different wavelengths of sunlight can modulate the viability of keratinocytes (Skin cells), and the metabolism. Red light, particularly, affects oxygen consumption during three days post-irradiation and enhances fatty acid oxidation.
Selected by Rickson Ribeiro, Marcus OliveiraCategories: biochemistry, biophysics, cell biology
Why this preprint is important:
Understand how different wavelengths impact our skin, the largest organ of human body, is of crucial importance. Some wavelengths of sunlight have a negative effect, such as UVA which causes DNA damage, while other wavelengths can have positive effects such as red light in promoting cell proliferation [4,5]. However, the specific effects of each wavelength in physiology of our skin cells is an open question. With that in mind, this study is important as it evaluates the effects of different wavelengths present in sunlight on keratinocytes and, specifically, how these impact their viability and energy metabolism.
Background:
Throughout evolutionary history, several organisms developed mechanisms to sense the sunlight and respond to it. Sunlight is composed of ultraviolet A (UVA; approximately 320 up to 400 nm), visible light (400 up to 700 nm), and near-infrared (700 up to 1100 nm) [1,2].
Sunlight photons can interact with different ways with matter. In human body, more specifically in the skin, different molecules can absorb radiation with different wavelengths, however, the effects caused by absorption is of medical interest and the subject of many studies.
Mitochondria are an intracellular organelle responsible for cellular energy transformation to maintain cell homeostasis. These structures have photosensitizers, such as a prosthetic group (heme) in cytochrome c oxidase (Complex IV), capable of absorbing radiations in the wavelength range of 600 up to 1100 nm which increase the electron transport, the proton gradient, ATP synthesis [3]. In this pre-print, the authors provide information about the interaction of different wavelengths of sunlight in keratinocyte viability and the metabolic pathway influenced by red light irradiation.
Key findings:
Effects of different wavelengths on keratinocyte viability.
In this study, to evaluate keratinocyte viability, the authors selected three methods (MTT, CVS, NRS) to verify the effects of exposition of 36 J/cm² of different wavelengths of light (UVA, Blue, Green, Red). The most significatively effect observed was caused by UVA which resulted in loss of cell viability at 48 hours post-exposure (Confirmed by all methods tested) and was maintained at 72 hours post-exposure. With light in green range, a significant decrease of keratinocyte viability was found in MTT and CVS at 48- and 72-hours post-exposure. Lastly, with light in the red range, the authors observed enhanced CVS intensity, indicating keratinocyte proliferation at 48- and 72-hours post-exposure. Based on all this, the authors suggest the keratinocytes respond differently to the same dose of light at distinct wavelengths.
Red light increases intact cell oxygen consumption up to two days post-exposure.
Next, the authors evaluated the cell oxygen consumption rate (OCR), after irradiation. Increased intact cell oxygen consumption was detected for the red wavelength and then was tested at different intensities (0, 6, 24, 36 and 150 J/cm²). It turned out that exposure to red light has a long-lasting effect and that OCR increases in a dose-dependent manner, maintained for over 2 days.
Red light exposure does not change the quantity or activity of components of oxidative phosphorylation in mitochondria.
The authors quantified the components of oxidative phosphorylation (Complex I to V) in mitochondria using the western-blot method. Their findings suggest that none of these parameters were significantly altered by red light. The authors note that: “ the respiratory enhancement observed in intact cells is not centered on a mitochondrial regulatory mechanism, a probably therefore involves modulation of cytosolic metabolic pathways upstream of oxidative phosphorylation”.
Enhance of fatty acid oxidation of keratinocytes after red light irradiation.
Finally, fatty acid oxidation was measured. For this, an inhibitor of CPT-1 (Etomoxir) was used to assess the contribution of beta oxidation on respiration. The authors claim that oxygen consumption rates were abrogated in red light-irradiated cells, indicating that increase CPT-1-dependent fatty acid oxidation is the mechanism by which red light promotes enhanced oxygen consumption in intact cells.
Questions and comments:
Major aspects
Q1: Could the authors elaborate why they used the dose of 36 J/cm²?
Q2: The radiation emitted by LED devices does not present some physical characteristics such as coherence and collimation (radiation with parallel and in-phase beams) similar to the sunlight. Could the authors describe the LED device, whether it was a set of LEDs or a single lamp to illuminate the entire board.
Q3: Related to Q2, are the LED devices positioned perpendicularly or inclined? Was the radiation capable of irradiating the entire area of the cells, and were the doses applied at each point in the same way?
Q4: In section 2.8, in the description of the statistical analysis, one-way ANOVA was used; however, it does not mention the normality test to understand the distribution of the data to choose the analysis test. Could the authors perhaps insert a normality test in the statistical analysis to determine the type of statistical test (parametric or non-parametric) to be applied? Maybe a non-parametric test (kruskal-Wallis test) could be more interesting due to the low number of samples.
Q5: In figure 9D, could the authors describe what the FA-dependent OCR is?
Q6: In figures 8 and 9, the color palette of graphs B, C, D and E could be changed to follow the same pattern as graph A. In my opinion, this would make the results easier to view and compare.
Q7: In figure 9C, it seems like the color pattern and axis legend were unintentionally mixed since red represents the irradiated group, and grey the non-irradiated (So: Dose: 0, 36, 0, 36/ Etomoxir: -, -, +, +). Could the authors review this graph perhaps, and, with this in mind, look at figure 9D and 9E too?
Minor aspects
Q8: In section 2.3, regarding the description of the viability assays, it is mentioned that the reagents were added at 2, 48, and 72 hours. However, in the graphs presented in Figure 1, the 2-hour time point does not appear to be included. Could you kindly clarify why this data was not presented?
Q9: Regarding Q8, it might be interesting to include a 24-hour time point for each viability assay in order to provide a more comprehensive overview of cell viability over time.
Q10: Figure 5 shows asterisks on the graphs for complexes I, IV, and V, suggesting statistically significant differences based on the Tukey test. Could you kindly clarify what these specific differences represent?
Disclaimer:
For the redaction of this report, was used the google translate and Grammarly.
References:
[1] I. Kohli, S. Chaowattanapanit, T. F. Mohammad, C. L. Nicholson, S. Fatima, G. Jacobsen, N. Kollias, H. W. Lim, I. H. Hamzavi.Synergistic effects of long-wavelenghts ultraviolet A1 and visible light on pigmentation and Erythema, Br J. Dermatol. 178(5) (2018) e357. Doi: https://doi.org/10.1111/bjd.16614
[2] W-T Huang, V. Rajendran, M-H. Chan, M. Hsiao, H. Chang, R-S Liu. Near-infrared Windows I and II phosphors for theragnostic applications: Spectroscopy, bioimaging, and light-emitting diode photobiomodulation. Adv. Opt. Mater. 11(1) (2022) 2202061. Doi: https://doi.org/10.1002/adom.202202061
[3] M. R. Hamblin. Mechanisms and Mitochrondial redox signaling in photobiomodulation. Photochem. Photobiol1 94(2) (2018) 199-212 Doi: https://doi.org/10.1111/php.12864
[4] J. Cadet, M. Berger, T. Douki, B. Morin, S. Raoul, J. Ravanat, S. Spinelli. Effects of UV and visible radiation on DNA-final base damage. Biol. Chem. 1997.
[5] M. A. Herrera, A. R. Ribas, P. E. Costa, M. S. Baptista. Red-light photons on skin cells and the mechanism of photobiomodulation. Frontiers. 5 (2024). Doi:https://doi.org/10.3389/fphot.2024.1460722
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This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
| List by | Dey Lab, Amanda Haage |






