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

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

  • Biochem Pharmacol. 2026 Apr:246:117729. doi: 10.1016/j.bcp.2026.117729.
Yujie Li 1,  Tingru Dong 1,  Jiamin Wu 1,  Fenglan Yang 1,  Shiyu Jin 1,  Renxue Xiong 2,  Meiya Li 3,  Xiuzu Song 4,  Cuiping Guan 5
Affiliations

Affiliations

  • 1 Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China.
  • 2 Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China.
  • 3 Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
  • 4 Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China. Electronic address: [email protected].
  • 5 Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China. Electronic address: [email protected].
PMID: 41571202 DOI: 10.1016/j.bcp.2026.117729
Abstract

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.

Keywords

Androgenetic alopecia; CYP19A1; Dermal papilla cells; MitoQ; Mitochondrial dysfunction.

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