Parthenolide reduces senescence and skin fibrosis in scleroderma models
The compound targets Ero1L to stabilize contacts between mitochondria and the endoplasmic reticulum, mitigating tissue damage in cells and mice.
In mice with bleomycin-induced localized scleroderma and cultured human dermal fibroblasts, researchers found that parthenolide alleviated cellular senescence and skin fibrosis. Electron microscopy revealed abnormal mitochondria-associated endoplasmic reticulum membranes with elevated calcium transport and numbers in scleroderma lesions. Parthenolide repaired mitochondrial damage and regulated the IP3R1/Grp75/VDAC1 complex in both cell and animal models. Molecular screening identified Ero1L as the drug target, binding specifically at the ARG-449 residue. Ero1L knockdown mirrored the antifibrotic and anti-senescence actions of the compound, whereas Ero1L overexpression blocked them. Finally, a controlled-release thermosensitive hydrogel delivering parthenolide nanoparticles showed therapeutic efficacy in the mouse model.
Why it matters
Targeting inter-organelle communication between the endoplasmic reticulum and mitochondria provides a potential strategy to counter cellular senescence and pathological tissue remodeling.
Caveats
The findings are limited to cultured cells and a chemically induced mouse model, requiring further study before translation to human patients.
- ERO1A knockdown
- ERO1A overexpression
- Parthenolide
- Cellular senescence
- Mitochondrial dysfunction
- Mitochondrial biogenesis (PGC-1α)
- TGF-β signalling
- ERO1A
- HSPA9
- ITPR1
- VDAC1
- Localized scleroderma
The paper
Targeting Ero1L by Parthenolide Alleviates Cellular Senescence and Fibrosis of Localized Scleroderma by Regulating Mitochondria-Associated Endoplasmic Reticulum Membranes Stabilization
Wang F, Xing R, Xie M et al.
Aging Cell · 30 Sep 2026