MT-CO2 Dysregulation in Alzheimer’s Disease and Its Modulation by Photobiomodulation: Implications for Mitochondrial Function

Mitochondrial dysfunction contributes to Alzheimer’s disease (AD), but the roles of individual respiratory-chain proteins remain incompletely understood. We examined mitochondrially encoded cytochrome c oxidase subunit II (MT-CO2) and nuclear encoded succinate dehydrogenase complex iron-sulfur subunit B (SDHB) in postmortem temporal cortex from cognitively normal (CN) individuals and patients with AD, Lewy body dementia/Parkinson’s disease (LBD/PD), or progressive supranuclear palsy (PSP). MT-CO2 abundance was lower in AD than in CN and LBD/PD, whereas SDHB was lower in AD than in CN, LBD/PD, and PSP. A significant protein × diagnosis interaction indicated distinct diagnostic-group patterns for MT-CO2 and SDHB. In BE(2)-C neuroblastoma cells, repeated 650 nm red-light and 808 nm near-infrared (NIR) photobiomodulation increased MT-CO2 abundance, with the largest responses following 10- and 15-min exposures. shRNA-mediated MT-CO2 reduction impaired Complex IV-dependent respiration and attenuated the bioenergetic response to 808 nm treatment. Photobiomodulation did not significantly alter mitochondrially encoded MT-CO1 or MT-CO3 abundance. These findings identify alterations in MT-CO2 and SDHB in AD temporal cortex and demonstrate that MT-CO2 contributes to Complex IV-dependent respiration and photobiomodulation-associated bioenergetic enhancement. Because mitochondrial content was not independently measured, the tissue findings cannot distinguish broader mitochondrial loss from protein-specific dysregulation.