PUBLICATION

Caveolae sense oxidative stress through membrane lipid peroxidation and cytosolic release of CAVIN1 to regulate NRF2

Authors
Wu, Y., Lim, Y.W., Stroud, D.A., Martel, N., Hall, T.E., Lo, H.P., Ferguson, C., Ryan, M.T., McMahon, K.A., Parton, R.G.
ID
ZDB-PUB-230302-38
Date
2023
Source
Developmental Cell   58(5): 376-397.e4 (Journal)
Registered Authors
Hall, Thomas, Lim, Ye-Wheen, Parton, Robert G.
Keywords
CAVIN1, NRF2, caveolae, cell death, ferroptosis, lipid peroxidation, oxidative stress
MeSH Terms
  • RNA-Binding Proteins/metabolism
  • Oxidative Stress
  • Caveolae*/metabolism
  • NF-E2-Related Factor 2*/metabolism
  • Zebrafish/metabolism
  • Animals
  • Lipid Peroxidation
(all 7)
PubMed
36858041 Full text @ Dev. Cell
Abstract
Caveolae have been linked to many biological functions, but their precise roles are unclear. Using quantitative whole-cell proteomics of genome-edited cells, we show that the oxidative stress response is the major pathway dysregulated in cells lacking the key caveola structural protein, CAVIN1. CAVIN1 deletion compromised sensitivity to oxidative stress in cultured cells and in animals. Wound-induced accumulation of reactive oxygen species and apoptosis were suppressed in Cavin1-null zebrafish, negatively affecting regeneration. Oxidative stress triggered lipid peroxidation and induced caveolar disassembly. The resulting release of CAVIN1 from caveolae allowed direct interaction between CAVIN1 and NRF2, a key regulator of the antioxidant response, facilitating NRF2 degradation. CAVIN1-null cells with impaired negative regulation of NRF2 showed resistance to lipid-peroxidation-induced ferroptosis. Thus, caveolae, via lipid peroxidation and CAVIN1 release, maintain cellular susceptibility to oxidative-stress-induced cell death, demonstrating a crucial role for this organelle in cellular homeostasis and wound response.
Genes / Markers
Figures
No images available
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Wu, Y., Lim, Y.W., Stroud, D.A., Martel, N., Hall, T.E., Lo, H.P., Ferguson, C., Ryan, M.T., McMahon, K.A., Parton, R.G. (2023) Caveolae sense oxidative stress through membrane lipid peroxidation and cytosolic release of CAVIN1 to regulate NRF2. Developmental Cell. 58(5):376-397.e4.