ACOD1 Deficiency Promotes DDX1 Methylation-Mediated Mitochondrial Dysfunction And Dermal Papilla Cell Senescence In Androgenetic Alopecia

This study investigates the role of ACOD1 in androgenetic alopecia (AGA), highlighting its impact on dermal papilla cell (DPC) senescence. The research shows that ACOD1 deficiency leads to increased DDX1 methylation, resulting in mitochondrial dysfunction and DPC senescence, which are key factors in AGA pathogenesis. The study utilized various methods, including RNA sequencing and metabolomic analysis, to demonstrate that ACOD1 knockdown exacerbates mitochondrial issues and cellular aging, while its overexpression mitigates these effects. Additionally, the study found that exogenous 4-octyl itaconate (4-OI) supplementation can reduce DDX1 methylation, improve mitochondrial function, enhance cell proliferation, and reduce hair loss in AGA mice. These findings suggest that targeting ACOD1 and using 4-OI could be promising therapeutic strategies for treating AGA.