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

Y Wu; YW Lim; DA Stroud; N Martel; TE Hall; HP Lo; C Ferguson; MT Ryan; KA McMahon; RG Parton

Journal article

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

Y Wu, YW Lim, DA Stroud, N Martel, TE Hall, HP Lo, C Ferguson, MT Ryan, KA McMahon, RG Parton

Developmental Cell | Published : 2023

DOI: 10.1016/j.devcel.2023.02.004

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 CAVI..

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University of Melbourne Researchers

David Stroud Author

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Grants

Awarded by Institute for Mind and Body, University of Chicago

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (grants APP1140064 and APP1150083 and fellowship APP1156489 to R.G.P.; grants APP1125390 and APP1140906 to M.T.R. and D.A.S. and fellowship APP1140851 to D.A.S.) . R.G.P. is an Australian Research Council laureate fellow (FL210100107) . The authors acknowledge the use of the Microscopy Australia Research Facility at the Center for Microscopy and Microanalysis at the University of Queensland. Confocal microscopy was performed at the Australian Cancer Research Foundation (ACRF)/Institute for Molecular Bioscience (IMB) Dynamic Imaging Facility for Cancer Biology with funding from the ACRF. We thank the Monash FlowCore and the Monash University Biomedical Proteomics Facility for the provision of instrumentation, training, and technical support.