Oxidative photocatalysis on membranes triggers non-canonical pyroptosis

Lee, C; Park, M; Wijesinghe, WCB; Na, S; Lee, CG; Hwang, E; Yoon, G; Lee, JK; Roh, DH; Kwon, YH; Yang, J; Hughes, SA; Vince, JE; Seo, JK; Min, D; Kwon, TH

Author(s): Lee, C; Park, M; Wijesinghe, WCB; Na, S; Lee, CG; Hwang, E; Yoon, G; Lee, JK; Roh, DH; Kwon, YH; Yang, J; Hughes, SA; Vince, JE; Seo, JK; Min, D; Kwon, TH;
Details: Publication Year 2024-05-13,Volume 15,Issue #1,Page 4025
Journal Title: Nature Communications
Abstract: Intracellular membranes composing organelles of eukaryotes include membrane proteins playing crucial roles in physiological functions. However, a comprehensive understanding of the cellular responses triggered by intracellular membrane-focused oxidative stress remains elusive. Herein, we report an amphiphilic photocatalyst localised in intracellular membranes to damage membrane proteins oxidatively, resulting in non-canonical pyroptosis. Our developed photocatalysis generates hydroxyl radicals and hydrogen peroxides via water oxidation, which is accelerated under hypoxia. Single-molecule magnetic tweezers reveal that photocatalysis-induced oxidation markedly destabilised membrane protein folding. In cell environment, label-free quantification reveals that oxidative damage occurs primarily in membrane proteins related to protein quality control, thereby aggravating mitochondrial and endoplasmic reticulum stress and inducing lytic cell death. Notably, the photocatalysis activates non-canonical inflammasome caspases, resulting in gasdermin D cleavage to its pore-forming fragment and subsequent pyroptosis. These findings suggest that the oxidation of intracellular membrane proteins triggers non-canonical pyroptosis.
Publisher: Springer Nature
Keywords: *Pyroptosis; *Oxidation-Reduction; Humans; *Inflammasomes/metabolism; *Membrane Proteins/metabolism; Oxidative Stress; Catalysis; Endoplasmic Reticulum Stress; Hydrogen Peroxide/metabolism; Phosphate-Binding Proteins/metabolism; Hydroxyl Radical/metabolism; Mitochondria/metabolism; Intracellular Membranes/metabolism; Intracellular Signaling Peptides and Proteins/metabolism; Mice; Animals; Photochemical Processes; Protein Folding; Caspases/metabolism; Gasdermins
Research Division(s): Inflammation
PubMed ID: 38740804
Publisher's Version: https://doi.org/10.1038/s41467-024-47634-5
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-024-47634-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: s41467-024-47634-5.pdf - (5.97MB, application/pdf)

Creation Date: 2024-05-20 07:53:38

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