Skin Pigmentation Associates With Reduced mtDNA Variant Burden in Photoexposed Skin.

Melanin, particularly eumelanin, is a key determinant of cutaneous photoprotection, yet its influence on mitochondrial DNA (mtDNA) stability remains poorly understood. This study investigated whether pigmentation is associated with somatic mtDNA variant burden and heteroplasmy in chronically photoexposed human skin. Targeted mitochondrial sequencing was performed on paired photoexposed forearm and photoprotected buttock biopsies from six aged male participants (three Black African and three White Northern European). Twenty-one high-confidence somatic mtDNA variants were identified. Photoexposed light skin possessed six-fold more variants than dark skin and exhibited a broader spectrum of variant classes, including single nucleotide variants, insertions, deletions, and dinucleotide substitutions. Light skin was enriched for C>T transitions and CC>TT dinucleotide substitutions, recognised signatures of chronic ultraviolet radiation (UVR) exposure, whereas dark skin displayed a more restricted variant profile dominated by a recurrent T414G substitution. Variants in light skin affected multiple oxidative phosphorylation genes and frequently reached moderate-to-high heteroplasmy, while dark skin contained predominantly low-impact variants with substantially lower heteroplasmy overall. These findings indicate that darker pigmentation is associated with reduced accumulation and clonal expansion of somatic mtDNA variants in chronically photoexposed skin. The results extend the recognised photoprotective effects associated with darker skin pigmentation beyond preservation of nuclear DNA and suggest that enhanced mitochondrial genomic stability may contribute to the greater resistance of darkly pigmented skin to UVR-induced photoageing.