MitoQ upregulates CYP19A1 to protect dermal papilla cells from DHT-induced mitochondrial dysfunction and apoptosis in androgenetic alopecia.

Androgenetic alopecia (AGA) is a progressive hair loss disorder characterized by follicular miniaturization primarily driven by dihydrotestosterone (DHT). Mitochondrial dysfunction in dermal papilla cells (DPCs) has emerged as a key pathological feature, yet the upstream regulatory mechanisms remain unclear. Our previous work revealed that the mitochondria-targeted antioxidant MitoQ upregulates CYP19A1 (aromatase) and alleviates AGA-like pathology. Here, we investigated whether CYP19A1 modulates mitochondrial function and mediates the protective effects of MitoQ. Using a DHT-induced AGA mouse model and DPCs with CYP19A1 knockdown or overexpression, we examined hormone profiles, mitochondrial activity, and hair growth-related factors. DHT markedly reduced CYP19A1 expression and increased inhibitory factors such as DKK1, TGF-β, and IL-6, whereas CYP19A1 overexpression or MitoQ pretreatment reversed these effects. Both CYP19A1 and MitoQ decreased mitochondrial reactive oxygen species (mtROS), improved respiratory capacity, and preserved mitochondrial morphology. Importantly, our findings reveal a previously unrecognized aromatase-mitochondria cross-talk in hair-follicle cells, whereby CYP19A1-derived estrogens sustain mitochondrial homeostasis under androgenic stress. MitoQ amplifies this cross-talk through CYP19A1 activation, restoring redox balance and mitochondrial integrity. Collectively, these results identify CYP19A1 as a pivotal regulator of mitochondrial resilience and suggest that the CYP19A1-mitochondrial axis represents a promising pharmacological target for treating AGA.