biostudies-literatureLee CKorea Electric Power CorporationNational Research Foundation of Korea (NRF)National Cancer CenterNational Cancer Center (NCC)Ministry of Knowledge Economy | Korea Institute of Energy Technology Evaluation and Planning (KETEP)National Research Foundation of KoreaKorea Electric Power Corporation (KEPCO)Ministry of Knowledge Economy | Korea Institute of Energy Technology Evaluation and Planning4025https://www.ebi.ac.uk/biostudies/studies/S-EPMC11091103biostudies-literatureUnknown15(1)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 Nature communicationsOxidative photocatalysis on membranes triggers non-canonical pyroptosis.PMC11091103R21XO02-8202230300102402021R1A2C2009504HA22C010100Wijesinghe WCBRoh DHSeo JKNa SYang JPark MHwang ELee CYoon GHughes SALee CGKwon YHVince JELee JKMin DKwon THfalseOxidative photocatalysis on membranes triggers non-canonical pyroptosis.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 2024-01-01T00:00:00Z2024 May2026-05-29T10:25:23.293Z2026-04-08T04:26:00.301ZS-EPMC110911033874080410.1038/s41467-024-47634-5