Emerging Roles of Ferroptosis in Skin Pathophysiology

Programmed cell death (PCD) is a hallmark of tissue homeostasis and numerous human diseases. Ferroptosis, a more recently discovered type of PCD, is uniquely dependent on enzymatically driven accumulation of specific hydroperoxy-phospholipid species and iron-dependent reduction-oxidation (redox) dysregulation. Emerging evidence suggests that ferroptosis plays a critical role in the pathogeneses of several dermatologic disorders, including infections, malignancies, and chronic inflammatory and autoimmune diseases. In this study, we review relevant regulatory mechanisms of ferroptosis, illustrate the challenges faced by the studies of ferroptosis, and highlight ferroptosis vulnerabilities in the redox balance of the skin. Furthermore, we review the link between ferroptosis and skin immunosurveillance and discuss ferroptosis functions in select skin diseases. Additional mechanistic studies that link ferroptosis to dysregulated cellular metabolism and proliferation, inflammation, and carcinogenesis will accelerate the emergence of new preventative and therapeutic strategies across a variety of dermatologic conditions.