Intracellular Mg²⁺ protects mitochondria from oxidative stress in human keratinocytes

Reactive oxygen species (ROS) are harmful for the human body, and exposure to ultraviolet irradiation triggers ROS generation. Previous studies have demonstrated that ROS decrease mitochondrial membrane potential (MMP) and that Mg²⁺ protects mitochondria from oxidative stress. Therefore, we visualized the spatio-temporal dynamics of Mg²⁺ in keratinocytes (a skin component) in response to H₂O₂ (a type of ROS) and found that it increased cytosolic Mg²⁺ levels. H₂O₂-induced responses in both Mg²⁺ and ATP were larger in keratinocytes derived from adults than in keratinocytes derived from newborns, and inhibition of mitochondrial ATP synthesis enhanced the H₂O₂-induced Mg²⁺ response, indicating that a major source of Mg²⁺ was dissociation from ATP. Simultaneous imaging of Mg²⁺ and MMP revealed that larger Mg²⁺ responses corresponded to lower decreases in MMP in response to H₂O₂. Moreover, Mg²⁺ supplementation attenuated H₂O₂-induced cell death. These suggest the potential of Mg²⁺ as an active ingredient to protect skin from oxidative stress.