Ruthenium(II) Lipid-Mimics Drive Lipid Phase Separation to Arouse Autophagy-Ferroptosis Cascade for Photoimmunotherapy.

ABSTRACT: Lipid-mediated phase separation is crucial for the formation of lipophilic spontaneous domain to regulate lipid metabolism and homeostasis, furtherly contributing to multiple cell death pathways. Herein, a series of Ru(II) lipid-mimics based on short chains or midchain lipids are developed. Among them, Ru-LipM with two dodecyl chains significantly induces natural lipid phase separation via hydrocarbon chain-melting phase transitions. Accompanied by the aggregation of Ru-LipM-labeled lipophilic membrane-less compartments, most polyunsaturated lipids are increased and the autophagic flux is retarded with the adaptor protein sequestosome 1 (p62). Upon low-dose irradiation, Ru-LipM further drives ferritinophagy, providing an additional source of labile iron and rendering cells more sensitive t

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC11744722 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature