MitoQ alleviates H2O2-induced mitochondrial dysfunction in keratinocytes through the Nrf2/PINK1 pathway

被引：0
作者：
Zhao, Yan [1 ]
Xiong, Renxue [1 ,2 ]
Jin, Shiyu [1 ]
Li, Yujie [1 ]
Dong, Tingru [1 ]
Wang, Wei [1 ,3 ]
Song, Xiuzu [1 ,2 ]
Guan, Cuiping [1 ,2 ]
机构：
[1] Zhejiang Chinese Med Univ, Hangzhou Hosp 3, Dept Dermatol, Hangzhou 310009, Peoples R China
[2] Hangzhou Third Peoples Hosp, Dept Dermatol, West Lake Rd 38, Hangzhou 310009, Peoples R China
[3] Hangzhou Third Peoples Hosp, Dept Pharm, Hangzhou 310009, Peoples R China
来源：
BIOCHEMICAL PHARMACOLOGY | 2025年 / 234卷
关键词：
MitoQ; Vitiligo; Keratinocyte; Oxidative stress; Mitophagy; PINK1/Parkin pathway; TARGETED ANTIOXIDANT MITOQ; OXIDATIVE STRESS; SIGNALING PATHWAY; DOUBLE-BLIND; VITILIGO; MITOPHAGY; INJURY; NRF2; MELANOCYTES; DISEASE;
D O I：
10.1016/j.bcp.2025.116811
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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 mu M H2O2 and/or 50 nM MitoQ, revealing that MitoQ mitigated the down- regulation of Nrf2, PINK1, and Parkin; reduced the nuclear translocation of Nrf2; and decreased the level of mitophagy induced by H2O2. 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 H2O2 and protect cells from damage. Therefore, our study offers experimental evidence and insights that may inform the development of therapeutic interventions for vitiligo.
引用
收藏
页数：13
相关论文
共 40 条
  • [1] Frisoli M.L., Essien K., Harris J.E., Vitiligo: mechanisms of pathogenesis and treatment, Annu. Rev. Immunol., 38, pp. 621-648, (2020)
  • [2] Laddha N.C., Dwivedi M., Mansuri M.S., Gani A.R., Ansarullah M., Ramachandran A.V., Et al., Vitiligo: interplay between oxidative stress and immune system, Exp. Dermatol., 22, 4, pp. 245-250, (2013)
  • [3] Mazurkiewicz J., Simiczyjew A., Dratkiewicz E., Kot M., Pietraszek-Gremplewicz K., Wilk D., Et al., Melanoma stimulates the proteolytic activity of HaCaT keratinocytes, Cell Commun. Signal, 20, 1, (2022)
  • [4] Barygina V., Becatti M., Lotti T., Moretti S., Taddei N., Fiorillo C., Treatment with low-dose cytokines reduces oxidative-mediated injury in perilesional keratinocytes from vitiligo skin, J. Dermatol. Sci., 79, 2, pp. 163-170, (2015)
  • [5] Prignano F., Pescitelli L., Becatti M., Di Gennaro P., Fiorillo C., Taddei N., Et al., Ultrastructural and functional alterations of mitochondria in perilesional vitiligo skin, J. Dermatol. Sci., 54, 3, pp. 157-167, (2009)
  • [6] Katayama H., Hama H., Nagasawa K., Kurokawa H., Sugiyama M., Ando R., Et al., Visualizing and modulating mitophagy for therapeutic studies of neurodegeneration, Cell, 181, 5, pp. 1176-1187.e16, (2020)
  • [7] Ashrafi G., Schlehe J.S., LaVoie M.J., Schwarz T.L., Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin, J. Cell Biol., 206, 5, pp. 655-670, (2014)
  • [8] Cen M., Ouyang W., Zhang W., Yang L., Lin X., Dai M., Et al., MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism, Redox Biol., 41, (2021)
  • [9] Barodia S.K., Creed R.B., Goldberg M.S., Parkin and PINK1 functions in oxidative stress and neurodegeneration, Brain Res. Bull., 133, pp. 51-59, (2017)
  • [10] Bakry O.A., Shoeib M., El Kady N., Attalla S., Re-appraisal of keratinocytes’ role in vitiligo pathogenesis, Indian J. Dermatol., 63, 3, pp. 231-240, (2018)
1234