Mitochondrial deoxyguanosine kinase depletion induced ROS causes melanocyte stem cell exhaustion and hair greying

TL;DR

This study shows that a lack of DGUOK in mitochondria causes hair greying by reducing melanocyte stem cells due to increased ROS.

Contribution

The study reveals a novel role of DGUOK in maintaining melanocyte stem cells through mtDNA integrity and ROS regulation.

Findings

Dguok depletion leads to premature hair greying due to loss of melanocyte stem cells.

DGUOK deficiency increases ROS and apoptosis in melanocyte stem cells.

NAC treatment reduces ROS and restores melanocyte stem cell populations.

Abstract

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.

The online version contains supplementary material available at 10.1186/s13619-025-00242-0.

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