Zhou Kaiyao, Wu Gangyun, Dong Rui, Kan Changhao, Xie Lin, Gao Lijuan, Li Hua, Sun Jianwei, Ning Wenxiu
Center for Life Sciences, Yunnan University, Kunming, Yunnan, 650500, China.
Yunnan Key Laboratory of Cell Metabolism and Diseases, Kunming, Yunnan, 650500, China.
Cell Regen. 2025 Jun 16;14(1):25. doi: 10.1186/s13619-025-00242-0.
Hair pigmentation is regulated by melanocyte stem cells (MeSCs) within the hair follicle. Mitochondrial dysfunction is associated with hair depigmentation, primarily due to defects in melanogenesis. However, the mechanisms by which mitochondria support MeSCs during hair pigmentation remain obscure. In this study, we investigated the role of mitochondrial deoxyguanosine kinase (DGUOK), which provides guanosine and adenosine nucleotides for mitochondrial DNA (mtDNA) replication, in hair pigmentation and MeSCs maintenance. Dguok depleted and conditional knockout mice exhibit premature hair greying. This phenotype was not due to impaired melanin production by melanocytes but was associated with a significant loss of MeSCs and mature melanocytes. Notably, Dguok deficiency decreased the expression of 13 mtDNA-encoded genes, increased the levels of reactive oxygen species (ROS) and apoptosis in MeSCs. Treatment with N-acetylcysteine (NAC), an ROS inhibitor, effectively mitigated the depigmentation and rejuvenated the MeSCs population. These findings underscore the critical role of DGUOK in regulating mtDNA integrity, which is vital for sustaining MeSCs and ensuring hair pigmentation, providing valuable insights that may inform therapeutic strategies for combating hair greying.
毛发色素沉着由毛囊内的黑素细胞干细胞（MeSCs）调控。线粒体功能障碍与毛发色素脱失有关，主要是由于黑素生成缺陷。然而，在毛发色素沉着过程中线粒体支持MeSCs的机制仍不清楚。在本研究中，我们研究了线粒体脱氧鸟苷激酶（DGUOK）在毛发色素沉着和MeSCs维持中的作用，DGUOK为线粒体DNA（mtDNA）复制提供鸟苷和腺苷核苷酸。Dguok基因敲除和条件性敲除小鼠表现出过早白发。这种表型并非由于黑素细胞产生黑色素受损，而是与MeSCs和成熟黑素细胞的显著丢失有关。值得注意的是，Dguok缺乏降低了13个mtDNA编码基因的表达，增加了MeSCs中活性氧（ROS）水平和细胞凋亡。用ROS抑制剂N-乙酰半胱氨酸（NAC）处理可有效减轻色素脱失并使MeSCs群体恢复活力。这些发现强调了DGUOK在调节mtDNA完整性中的关键作用，这对于维持MeSCs和确保毛发色素沉着至关重要，为对抗白发的治疗策略提供了有价值的见解。
