MitoQ alleviates HO-induced mitochondrial dysfunction in keratinocytes through the Nrf2/PINK1 pathway.

Shiyu Jin, Yan Zhao, Yujie Li, Wei Wang, Renxue Xiong, Tingru Dong, Xiuzu Song, Cuiping Guan

Journal: Biochemical pharmacology 2025;234():116811

PMID: 39978690

Full Text on Elsevier Science View on PubMed

Abstract

Oxidative stress plays a critical role in the pathogenesis of vitiligo by damaging keratinocytes, which disrupts their biological functions and influences the progression of the disease. MitoQ, a mitochondria-specific antioxidant, has the potential to prevent disorders associated with oxidative stress and to exert protective effects specifically on mitochondria. This study investigated the protective effects of MitoQ against oxidative stress in keratinocytes. We observed downregulated expression levels of Nrf2, PINK1, Parkin, and LC3 in vitiligo patients. HaCaT cells were treated with 900 μM HO and/or 50 nM MitoQ, revealing that MitoQ mitigated the downregulation of Nrf2, PINK1, and Parkin; reduced the nuclear translocation of Nrf2; and decreased the level of mitophagy induced by HO. Following the knockdown of NFE2L2 or PINK1 in HaCaT cells, we noted an increase in intracellular reactive oxygen species, changes in mitochondrial morphology, a dramatic decrease in the mitochondrial membrane potential, and a significant rise in cell death levels. In comparison to the group without NFE2L2 or PINK1 knockdown, MitoQ treatment failed to alleviate these conditions. These results suggest that MitoQ may regulate the PINK1/Parkin signaling pathway via Nrf2 to counteract mitochondrial oxidative stress induced by HO and protect cells from damage. Therefore, our study offers experimental evidence and insights that may inform the development of therapeutic interventions for vitiligo.

Address: Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China.; Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China.; Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Pharmacy, Hangzhou Third People's Hospital, Hangzhou 310009, China.; Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China. Electronic address: [email protected].; Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China. Electronic address: [email protected].

DOI: 10.1016/j.bcp.2025.116811

Link outs

Subscription / membership required

Full Text Sources:

MeSH Terms: Humans, NF-E2-Related Factor 2, Organophosphorus Compounds, Ubiquinone, Hydrogen Peroxide, Keratinocytes, Mitochondria, Signal Transduction, Protein Kinases, Oxidative Stress, HaCaT Cells, Dose-Response Relationship, Drug, Vitiligo, Antioxidants, Membrane Potential, Mitochondrial, Cell Line