Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of pigmentation. Among various hypotheses proposed for the pathogenesis of vitiligo, oxidative stress‐induced immune response that ultimately leads to melanocyte death remains most widely accepted. Oxidative stress which causes elevated levels of reactive oxygen species (ROS) can lead to dysfunction of molecules and organelles, triggering further immune response, and ultimately melanocyte death. In recent years, a variety of cell death modes have been studied, including apoptosis, autophagy and autophagic cell death, ferroptosis, and other novel modes of death, which will be discussed in this review in detail. Oxidative stress is also strongly linked to these modes of death. Under oxidative stress, ROS could induce autophagy by activating the Nrf2 antioxidant pathway of melanocytes. However, persistent stimulation of ROS might eventually lead to excessive activation of Nrf2 antioxidant pathway, which in turn will inactivate autophagy. Moreover, ferroptosis may be triggered by oxidative‐related transcriptional production, including ARE, the positive feedback loop related to p62, and the reduced activity and expression of GPX4. Therefore, it is reasonable to infer that these modes of death are involved in the oxidative stress response, and that oxidative stress also acts as an initiator for various modes of death through some complex mechanisms. In this study, we aim to summarize the role of oxidative stress in vitiligo and discuss the corresponding mechanisms of interaction between various modes of cell death and oxidative stress. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of vitiligo.

Introduction: Hydrogen sulfide (H₂S), a colorless, water soluble, flammable gas with a characteristic smell of rotten eggs, has been known as a highly toxic gas for several years. However, much like carbon monoxide (CO) and nitric oxide (NO), the initial negative perception of H₂S has developed with the discovery that H₂S is generated enzymatically in animals under normal conditions. With the result of this discovery, much more work is needed to elucidate the biologic effects of H₂S. In recent years, its cytoprotective properties have been recognized in multiple organs and tissues. In particular, H₂S plays important roles in combating oxidative species such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) and protect the body from oxidative stress. Therefore, this review discusses the biologic effect of H₂S and how it protects cells in various diseases by acting as an antioxidant that reduces excessive amounts of ROS and RNS. Ethics and dissemination: Ethical approval and informed consent are not required, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care. Conclusion: H₂S has been found to be cytoprotective in oxidative stress in a wide range of physiologic and pathologic conditions, an increasing number of therapeutic potentials of H₂S also have been revealed. However, there is still much debate on the clear mechanism of action of H₂S, so that the mechanisms of cell signaling that promote cellular survival and organ protection need to be further investigated to provide better H₂S-based therapeutics.

Autophagy is a process involving the self-digestion of components that participates in anti-oxidative stress responses and protects cells against oxidative damage. However, the role of autophagy in the anti-oxidative stress responses of melanocytes remains unclear. To investigate the role of autophagy in human epidermal melanocytes, we knocked down and overexpressed ATG7, the critical gene of autophagy, in normal human epidermal melanocytes. We demonstrated that ATG7-dependent autophagy could affect melanin content of melanocytes by regulating melanogenesis. Moreover, suppression of ATG7-dependent autophagy inhibits proliferation and promotes oxidative stress-induced apoptosis of melanocytes, whereas enhancement of ATG7-dependent autophagy protects melanocytes from oxidative stress-induced apoptosis. Meanwhile, deficiency of ATG7-dependent autophagy results in premature senescence of melanocytes under oxidative stress. Notably, we verified that ATG7-dependent autophagy could alter oxidative stress homeostasis by regulating reactive oxygen species (ROS) production, nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, and the activity of several antioxidant enzymes in melanocytes. In conclusion, our study suggested that ATG7-dependent autophagy is indispensable for redox homeostasis and the biological functions of melanocytes, such as melanogenesis, proliferation, apoptosis, and senescence, especially under oxidative stress.

Loss of melanocytes (MCs) is the most notable feature of vitiligo. Hence, it is critical to clarify the mechanisms of MC destruction in vitiligo. Apoptosis is most widely studied cell death pathways in vitiligo. In addition, the other two forms of cell death, conventional necrosis and autophagy seem to be involved in the death of vitiligo MCs under certain situations. Moreover, new types of regulated cell death including necroptosis, pyroptosis, and ferroptosis may also participate in the pathogenesis of vitiligo. Anoikis is likely to be connected with the death of detached MCs, which is provoked specifically by loss of anchorage. Primary phagocytosis, later called phagoptosis can execute death of viable cells, probably partly responsible for the loss of MCs in vitiligo. In this review, we aim to summarize the latest insights into various forms of MC death in vitiligo and discuss the corresponding mechanisms.

Vitiligo is an acquired depigmentation disorder affecting 0.5% to 2.0% of the global population¹ and is often psychologically devastating because the signs usually appear on the face and other visible areas. Disease progression is unpredictable and characterized by periods of disease inactivity interspersed with that of slow or rapid depigmentation, which is frequently indicative of worse prognosis and longer treatment course.² However, former criteria for defining disease activity was mostly based on small-scale studies.³ Therefore, novel markers for the clinical progression from large-scale prospective studies with long-term follow-up need to be identified to devise early intervention strategies.