Christopher Josie A, Breckels Lisa M, Crook Oliver M, Vazquez-Chantada Mercedes, Barratt Derek, Lilley Kathryn S
Cambridge Centre for Proteomics, Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, UK.
Cambridge Centre for Proteomics, Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, UK.
Mol Cell Proteomics. 2025 Jan;24(1):100888. doi: 10.1016/j.mcpro.2024.100888. Epub 2024 Nov 29.
Cells have many protective mechanisms against background levels of ionizing radiation orchestrated by molecular changes in expression, post-translational modifications, and subcellular localization. Radiotherapeutic treatment in oncology attempts to overwhelm such mechanisms, but radioresistance is an ongoing challenge. Here, global subcellular proteomics combined with Bayesian modeling identified 544 differentially localized proteins in A549 cells upon 6 Gy X-ray exposure, revealing subcellular-specific changes of proteins involved in ferroptosis, an iron-dependent cell death, suggestive of potential radioresistance mechanisms. These observations were independent of expression changes, emphasizing the utility of global subcellular proteomics and the promising prospect of ferroptosis-inducing therapies for combating radioresistance.
细胞具有许多针对背景水平电离辐射的保护机制，这些机制由表达、翻译后修饰和亚细胞定位的分子变化精心调控。肿瘤学中的放射治疗试图克服这些机制，但放射抗性仍是一个持续存在的挑战。在此，全球亚细胞蛋白质组学与贝叶斯建模相结合，鉴定出在6 Gy X射线照射后A549细胞中有544种差异定位的蛋白质，揭示了参与铁死亡（一种铁依赖性细胞死亡）的蛋白质的亚细胞特异性变化，提示了潜在的放射抗性机制。这些观察结果与表达变化无关，强调了全球亚细胞蛋白质组学的实用性以及铁死亡诱导疗法对抗放射抗性的广阔前景。
