Endoplasmic Reticulum Dysfunction: An Emerging Mechanism of Vitiligo Pathogenesis

Yongyi Xie,1,* Nanhui Wu,1,* Suwei Tang,1,* Zhiyu Zhou,1 Jiashe Chen,1 Jie Li,1 Fei Wu,1 Mingyuan Xu,1 Xiaoxiang Xu,1 Yeqiang Liu,1 Xin Ma1,2 1Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yeqiang Liu; Xin Ma, Shanghai Skin Disease Hospital, Institute of Dermatology, Baode Road 1278 Street, Shanghai, 200433, People’s Republic of China, Email 1500156@tongji.edu.cn; Nicole.ma@me.comAbstract: The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo.Keywords: vitiligo, endoplasmic reticulum, organelles, cellular interactions, oxidative stress