ROS and calcium signaling are critical determinant of skin pigmentation

Pigmentation is a protective phenomenon that shields skin cells from UV-induced DNA damage. Perturbations in pigmentation pathways predispose to skin cancers and lead to pigmentary disorders. These ailments impart psychological trauma and severely affect the patients' quality of life. Emerging literature suggests that reactive oxygen species (ROS) and calcium (Ca²⁺) signaling modules regulate physiological pigmentation. Further, pigmentary disorders are associated with dysregulated ROS homeostasis and changes in Ca²⁺ dynamics. Here, we systemically review the literature that demonstrates key role of ROS and Ca²⁺ signaling in pigmentation and pigmentary disorders. Further, we discuss recent studies, which have revealed that organelle-specific Ca²⁺ transport mechanisms are critical determinant of pigmentation. Importantly, we deliberate upon the possibility of clinical management of pigmentary disorders by therapeutically targeting ROS generation and cellular Ca²⁺ handling toolkit. Finally, we highlight the key outstanding questions in the field that demand critical and timely attention. Although an important role of ROS and Ca²⁺ signaling in regulating skin pigmentation has emerged, the underlying molecular mechanisms remain poorly understood. In future, it would be vital to investigate in detail the signaling cascades that connect perturbed ROS homeostasis and Ca²⁺ signaling to human pigmentary disorders.