Abstract 357: Reducing reagent-resistant transferrin receptor 1 dimer is a specific marker for ferroptosis

Abstract

Abstract Ferroptosis is an iron-dependent cell death caused by the catastrophic accumulation of lipid peroxidation. Despite the burgeoning ferroptosis research, there remains a void for an intrinsic and comprehensive ferroptosis indicator. Here we reported a simple and cost-effective way to detect ferroptotic cell death using reducing reagent-resistant (RRR) transferrin receptor 1 (TfR1). The TfR1 RRR dimer strongly correlates with ferroptosis induced by various ferroptosis-inducing conditions and relies on lipid peroxidation, which is not observed in other types of cell death. Through iron-overloading and tumor xenograft mouse models, we validate the in vivo ferroptosis detection using this technique. Furthermore, we identify the presence of TfR1 RRR dimers in extracellular vesicles isolated from the plasma of mice with ferroptosis-related diseases. Since TfR1 is a ubiquitously expressed protein, the increase of TfR1 RRR dimer can be used as a specific and endogenous ferroptosis marker with potential clinical applications. Citation Format: Jianping He, Mackenzie Kelleher, Lucas Reynolds, Hannah Tanczos, Zhengrong Huang, Brett McLaughlin, Wesley Huang, Lauren Pope, Geraldine Veeckmans, Tom Vanden Berghe, Scott J. Dixon, Yatrik Shah, Zachary T. Schafer. Reducing reagent-resistant transferrin receptor 1 dimer is a specific marker for ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 357.