Viewpoint 3

The document discusses the complexities of vitiligo, a condition characterized by the loss of melanocytes, the cells responsible for skin pigmentation. Despite advances in understanding, many aspects of vitiligo remain unclear, including the exact cause of melanocyte disappearance and whether other epidermal or systemic cells are affected. The document highlights that oxidative stress, both localized and systemic, is a significant factor in vitiligo pathogenesis. It also suggests that non-epidermal cells are involved and that oxidative stress may arise from various sources, including intrinsic cellular damage and metabolic dysfunction. The paper proposes that membrane alterations, particularly involving cholesterol and cardiolipin, could be a unifying mechanism for the various cellular impairments observed in vitiligo. This includes affecting the stability and activity of the respiratory chain, increasing reactive oxygen species (ROS) production, and promoting membrane lipid peroxidation. These changes may lead to altered signal transduction and the generation of new, immunogenic antigens, potentially triggering immune activation. The document also speculates on the role of the hair follicle niche in melanocyte production and the possible impact of vitiligo on this process. The effectiveness of cardiolipin components or lipoic acid supplementation in experimental models supports the proposed hypothesis.