Frequency-Selective Terahertz Irradiation Activates Mitochondrial Biogenesis

Mitochondria play a central role in cellular energy metabolism, survival, and apoptosis, with their dysfunction implicated in numerous diseases, including neurodegenerative and age-related disorders. Modulating mitochondrial function therefore represents a promising therapeutic strategy. In this study, we demonstrate that high-frequency terahertz (THz) irradiation elicits frequency-specific effects on mitochondrial biogenesis. Through MitoTimer and MitoTracker assays, we observed that irradiation at 34.5 THz significantly enhanced mitochondrial biogenesis, an effect not observed at 36.1 THz. Electrophysiological and molecular analyses revealed that 34.5 THz irradiation elevates intracellular calcium flux and activates the calcium-mediated PGC-1α-NRF1/2-TFAM pathway, leading to increased cellular energy production and oxygen consumption. Computational modeling suggested a resonant coupling mechanism in which 34.5 THz irradiation interacts with the bending vibration of the glutamate C-C-C bond at the narrowest region of the calcium ion channel pore, thereby lowering the energy barrier for calcium influx. Our findings reveal a noninvasive, frequency-specific mitochondrial modulation by THz irradiation, which may offer a promising therapeutic avenue for addressing mitochondrial dysfunction.