Photobiomodulation (PBM) has been investigated for its interactions with mitochondrial bioenergetics, particularly its influence on the electron transport chain (ETC).
An overview of the available literature presented several key findings regarding how specific wavelengths may positively or negatively regulate mitochondrial ETC complexes.
Wavelength Regulation Across Mitochondrial Complexes
Several studies have explored how different wavelengths used in photobiomodulation may modulate mitochondrial complexes. Pastore et al. (2000) demonstrated in vitro that He-Ne laser irradiation at 632.8 nm influenced the activity of cytochrome c oxidase (Complex IV), altering ATP production, while no changes were observed in the activity of Complex III or cytochrome c. Lunova et al. (2019) investigated the effects of various wavelengths on mitochondrial function and found that blue laser light (398 nm) inhibited cytochrome c oxidase, while red light (650 nm) promoted its activation. In contrast, green light (505 nm) showed minimal effects under the tested conditions.
Ravera et al. (2019) reported that irradiation with 1064 nm light stimulated Complexes I, III, IV, and V, while Complex II and mitochondrial matrix enzymes remained unaffected. The authors noted that these effects did not appear to result from thermal changes, suggesting a photobiological mechanism. Cardoso et al. (2022) examined the effects of chronic transcranial PBM at 810 nm in aged rats and observed an increase in cytochrome c oxidase activity. This effect was associated with a partial reversal of age-related mitochondrial decline in the brain.
Barolet et al. (2023) reviewed existing evidence and emphasized that red and near-infrared (NIR) light primarily target cytochrome c oxidase due to its absorption peaks between 600–700 nm and 760–940 nm. They proposed that light may dissociate inhibitory nitric oxide (NO) from the enzyme, thereby restoring mitochondrial respiration and ATP synthesis. Sanderson et al. (2018) found that while 810 nm NIR light increased cytochrome c oxidase activity, wavelengths at 750 nm and 950 nm decreased it. These COX-inhibitory wavelengths were associated with neuroprotective effects in a model of cerebral reperfusion injury.
Pope and Denton (2023) studied the response of isolated mitochondria to 808 nm NIR exposure. Their findings indicated enhanced activity of Complex IV, reduced activity of Complex III, and no changes in Complex II. Interestingly, the response of Complex IV did not follow an irradiance reciprocity pattern, suggesting a mechanism not purely photochemical in nature. O’Donnell et al. (2023) investigated the effects of transcranial infrared laser stimulation at 1064 nm in older adults with bipolar disorder. Compared to sham treatment, the intervention increased levels of oxidized cytochrome c oxidase and cerebral oxygenation, suggesting potential support for mitochondrial oxidative function in the prefrontal cortex.
Silveira et al. (2019) evaluated the effects of PBM using 660 nm light on mitochondria from brain, muscle, and glioma cells. The results demonstrated modulation of respiratory complex activity in a dose- and time-dependent manner, with specific changes observed in Complexes I, II, and IV. Finally, Amaroli et al. (2021) reported that 980 nm light produced varying effects depending on power levels. At low powers, Complexes III and IV were inhibited; higher powers (0.8–1.1 W) enhanced ATP production and complex activity. Their earlier research (2016) also indicated that 808 nm light could stimulate Complexes III and IV, without affecting Complexes I and II.
Conclusion
The existing literature suggests that PBM can influence mitochondrial function in a wavelength-, dose-, and time-dependent manner. Different mitochondrial complexes may respond differently depending on the parameters used, and both stimulatory and inhibitory effects have been reported. Continued investigation may help refine PBM protocols for potential therapeutic applications.
References:
Amaroli A, Pasquale C, Zekiy A, Utyuzh A, Benedicenti S, Signore A, Ravera S. Photobiomodulation and Oxidative Stress: 980 nm Diode Laser Light Regulates Mitochondrial Activity and Reactive Oxygen Species Production. Oxidative medicine and cellular longevity, 2021:6626286. doi: 10.1155/2021/6626286
Amaroli A, Ravera S, Parker S, Panfoli I, Benedicenti A, Benedicenti S. An 808-nm Diode Laser with a Flat-Top Handpiece Positively Photobiomodulates Mitochondria Activities. Photomedicine and laser surgery, 2016;34(11):564–571. doi: 10.1089/pho.2015.4035
Barolet AC, Villarreal AM, Jfri A, Litvinov IV, Barolet D. Low-Intensity Visible and Near-Infrared Light-Induced Cell Signaling Pathways in the Skin: A Comprehensive Review. Photobiomodulation, photomedicine, and laser surgery, 2023;41(4):147–166. doi: 10.1089/photob.2022.0127
Cardoso FDS, Barrett DW, Wade Z, Gomes da Silva S, Gonzalez-Lima F. Photobiomodulation of Cytochrome c Oxidase by Chronic Transcranial Laser in Young and Aged Brains. Front Neurosci. 2022;16:818005. doi: 10.3389/fnins.2022.818005.
Lunova M, Smolková B, Uzhytchak M, Janoušková KŽ, Jirsa M, Egorova D, et al. Light-induced modulation of the mitochondrial respiratory chain activity: possibilities and limitations. Cellular and molecular life sciences : CMLS. 2020;77(14):2815–2838. doi:10.1007/s00018-019-03321-z
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O’Donnell CM, Barrett DW, O’Connor P, Gonzalez-Lima F. Prefrontal photobiomodulation produces beneficial mitochondrial and oxygenation effects in older adults with bipolar disorder. Frontiers in neuroscience, 2023;17:1268955. doi:10.3389/fnins.2023.1268955
Pastore D, Greco M, Passarella S. Specific helium-neon laser sensitivity of the purified cytochrome c oxidase. International journal of radiation biology. 2000;76(6):863–870. doi:10.1080/09553000050029020
Ravera S, Ferrando S, Agas D, et al. 1064 nm Nd:YAG laser light affects transmembrane mitochondria respiratory chain complexes. J. Biophotonics. 2019;12:e201900101. doi:10.1002/jbio.201900101
Silveira PCL, Ferreira GK, Zaccaron RP, Glaser V, Remor AP, Mendes C, et al. Effects of photobiomodulation on mitochondria of brain, muscle, and C6 astroglioma cells. Medical engineering & physics, 2019;71:108–113. doi:10.1016/j.medengphy.2019.05.008