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PALP: An imaging method for detecting and quantifying polyunsaturated phospholipids via peroxidation

View ORCID ProfileYilong Zou, Emily T. Graham, Yuwei Huang, Wendy Salmon, Li Yu, Stuart L. Schreiber
doi: https://doi.org/10.1101/2020.04.11.037218
Yilong Zou
1Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA
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  • For correspondence: stuart_schreiber@harvard.edu yzou@broadinstitute.org
Emily T. Graham
1Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA
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Yuwei Huang
2School of Life Sciences, Tsinghua University, Beijing, 100084, China
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Wendy Salmon
3Whitehead Institute for Biomedical Research, MIT, Cambridge, MA 02142, USA
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Li Yu
2School of Life Sciences, Tsinghua University, Beijing, 100084, China
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Stuart L. Schreiber
1Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA
4Department of Chemistry and Chemical Biology, Harvard University, MA 02138, USA
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  • For correspondence: stuart_schreiber@harvard.edu yzou@broadinstitute.org
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ABSTRACT

Polyunsaturated phospholipids are essential for multiple cellular functions; however, their uncontrolled peroxidation leads to ferroptosis. Here we describe photochemical activation of membrane lipid peroxidation (PALP), which uses localized laser pulses to induce lipid peroxidation photochemically. While PALP bypasses enzymatic requirements for lipid peroxidation, the resulting BODIPY-C11-based signal is largely correlated with local polyunsaturated phospholipid concentration on membranes. This technique enables non-invasive reporting of lipid unsaturation levels and sensitivity to ferroptosis in live cells.

Competing Interest Statement

S.L.S. serves on the Board of Directors of the Genomics Institute of the Novartis Research Foundation (“GNF”); is a shareholder and serves on the Board of Directors of Jnana Therapeutics; is a shareholder of Forma Therapeutics; is a shareholder and advises Kojin Therapeutics, Kisbee Therapeutics, Decibel Therapeutics and Eikonizo Therapeutics; serves on the Scientific Advisory Boards of Eisai Co., Ltd., Ono Pharma Foundation, Exo Therapeutics, and F-Prime Capital Partners; and is a Novartis Faculty Scholar. Kojin Therapeutics in particular explores the medical potential of cell plasticity related to ferroptosis. Other authors declare no conflict of interest relevant to this study.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 12, 2020.
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PALP: An imaging method for detecting and quantifying polyunsaturated phospholipids via peroxidation
Yilong Zou, Emily T. Graham, Yuwei Huang, Wendy Salmon, Li Yu, Stuart L. Schreiber
bioRxiv 2020.04.11.037218; doi: https://doi.org/10.1101/2020.04.11.037218
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PALP: An imaging method for detecting and quantifying polyunsaturated phospholipids via peroxidation
Yilong Zou, Emily T. Graham, Yuwei Huang, Wendy Salmon, Li Yu, Stuart L. Schreiber
bioRxiv 2020.04.11.037218; doi: https://doi.org/10.1101/2020.04.11.037218

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