PALP: A rapid imaging technique for stratifying ferroptosis sensitivity in normal and tumor tissues in situ. Issue 1 (20th January 2022)

• Record Type: Journal Article
• Authors: Wang, Fengxiang; Graham, Emily T.; Naowarojna, Nathchar; Shi, Zhennan; Wang, Yuqi; Xie, Guanglei; Zhou, Lili; Salmon, Wendy; Jia, Jie-Min; Wang, Xi; Huang, Yuwei; Schreiber, Stuart L.; Zou, Yilong
• Is Part Of: Cell chemical biology. Volume 29:Issue 1(2022)
• Page Start: 157
• Page End: 170.e6
• Publication Date: 2022-01-20
• Subjects: ferroptosis sensitivity stratification -- cancer -- polyunsaturated lipid -- in situ quantitation -- imaging -- lipid peroxidation; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2021.11.001
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: Ferroptosis is an emerging cancer suppression strategy. However, how to select cancer patients for treating with ferroptosis inducers remains challenging. Here, we develop photochemical activation of membrane lipid peroxidation (PALP), which uses targeted lasers to induce localized polyunsaturated fatty acyl (PUFA)-lipid peroxidation for reporting ferroptosis sensitivity in cells and tissues. PALP captured by BODIPY-C11 can be suppressed by lipophilic antioxidants and iron chelation, and is dependent on PUFA-lipid levels. Moreover, we develop PALPv2, for studying lipid peroxidation on selected membranes along the z axis in live cells using two-photon microscopes. Using PALPv1, we detect PUFA-lipids in multiple tissues, and validate a PUFA-phospholipid reduction during muscle aging as previously reported. Patterns of PALPv1 signals across multiple cancer cell types in vitro and in vivo are concordant with their ferroptosis susceptibility and PUFA-phospholipid levels. We envision that PALP will enable rapid stratification of ferroptosis sensitivity in cancer patients and facilitate PUFA-lipid research. Graphical abstract: Highlights: Targeted high-power laser induces lipid peroxidation on cellular membranes PALP signals are dependent on polyunsaturated phospholipid levels on membranes PALPv1 can assist estimating sensitivity to ferroptosis in cells and tissue sections PALPv2 enables studying lipid peroxidation on selected cellular membranes Abstract : Selecting the right cancer patients for ferroptosis-inducing therapies remains difficult. Wang et al. have developed an imaging technique, photochemical activation of membrane lipid peroxidation (PALP), which uses the propensity of polyunsaturated phospholipids to undergo laser-induced peroxidation to estimate ferroptosis susceptibility in live cells and tissues in situ .