FUNDC1 protects skin against UVA damage through mitophagy and P53 stability
Researchers identified a molecular pathway where FUNDC1 preserves mitochondrial quality and works with BAZ1B to regulate P53 during skin photoaging.
In human dermal fibroblasts and mouse skin, researchers observed that chronic ultraviolet A exposure reduces levels of FUNDC1. Knocking down FUNDC1 worsened photoaging phenotypes, impaired mitochondrial function, and altered mitophagy activity. In contrast, overexpressing FUNDC1 alleviated these defects both in vitro and in vivo. Rapamycin partially reversed the damage caused by FUNDC1 knockdown, while the mitophagy inhibitor Mdivi-1 reduced the benefits of FUNDC1 overexpression. Mechanistically, UVA exposure upregulated miR-137-3p, which repressed FUNDC1 through its 3'UTR. FUNDC1 also helped regulate proteasome-dependent P53 stability alongside BAZ1B. Analysis revealed that BAZ1B mediated P53 ubiquitination predominantly at the K292 site. In mice, BAZ1B knockdown diminished P53 ubiquitination and weakened FUNDC1-mediated defense against photoaging.
Why it matters
Mitochondrial dysfunction and impaired quality control are key drivers of ultraviolet-induced tissue aging. Identifying how FUNDC1 coordinates mitophagy and tumor suppressor stability clarifies how skin cells resist chronic environmental stress.
Caveats
The findings derive strictly from cultured cells and mouse models under controlled UVA exposures. Further studies must test whether these regulatory mechanisms translate to diverse human populations.
- BAZ1B knockdown
- FUNDC1 knockdown
- FUNDC1 overexpression
- Mdivi-1
- Rapamycin
- Ultraviolet a exposure
- Disabled macroautophagy
- Loss of proteostasis
- Mitochondrial dysfunction
- Mitophagy
- Ubiquitin–proteasome system
- p53–p21 pathway
The paper
FUNDC1 Attenuates UVA-Induced Skin Photoaging by Regulating Mitophagy and P53 Stability
Zhang C, Hou M, Wang N et al.
Antioxidants · 25 Aug 2026