“…Melanin synthesis represents a complex series of tightly regulated steps involving the consumption of oxygen and superoxide and the production and utilization of hydrogen peroxide, all carefully orchestrated within a well-organized organelle, the melanosome (37). Melanosomes progressively become more structurally or functionally disordered or both during melanomagenesis, evoking more ROS production and leading to an ongoing peroxide stress within the melanoma cell, especially when bound to Cu (22,28,31,96). Consistently, normal melanocytes efficiently abrogate an exogenous peroxide stress, whereas human melanoma cells are seriously impaired in their ability to do so and generate higher levels of reactive oxygen species (ROS) (74).…”