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. 2024 Oct 8;121(41):e2316450121.
doi: 10.1073/pnas.2316450121. Epub 2024 Oct 2.

Mechanosensitive fluorescence lifetime probes for investigating the dynamic mechanism of ferroptosis

Xing Liang  1 , Yuping Zhao  1 , Jun Yan  1 , Qian Zhang  1 , Tony D James  2   3 , Weiying Lin  1
Affiliations

Mechanosensitive fluorescence lifetime probes for investigating the dynamic mechanism of ferroptosis

Xing Liang et al. Proc Natl Acad Sci U S A. .

Abstract

Deciphering the dynamic mechanism of ferroptosis can provide insights into pathogenesis, which is valuable for disease diagnosis and treatment. However, due to the lack of suitable time-resolved mechanosensitive tools, researchers have been unable to determine the membrane tension and morphology of the plasma membrane and the nuclear envelope during ferroptosis. With this research, we propose a rational strategy to develop robust mechanosensitive fluorescence lifetime probes which can facilitate simultaneous fluorescence lifetime imaging of the plasma membrane and nuclear envelope. Fluorescence lifetime imaging microscopy using the unique mechanosensitive probes reveal a dynamic mechanism for ferroptosis: The membrane tension of both the plasma membrane and the nuclear envelope decreases during ferroptosis, and the nuclear envelope exhibits budding during the advanced stage of ferroptosis. Significantly, the membrane tension of the plasma membrane is always larger than that of the nuclear envelope, and the membrane tension of the nuclear envelope is slightly larger than that of the nuclear membrane bubble. Meanwhile, the membrane lesions are repaired in the low-tension regions through exocytosis.

Keywords: fluorescence lifetime imaging; fluorescence lifetime probes; mechanism of ferroptosis; membrane tension; nuclear envelope budding.

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Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

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