Global Proteomics Indicates Subcellular-Specific Anti-Ferroptotic Responses to Ionizing Radiation.

IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Molecular & Cellular Proteomics Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI:10.1016/j.mcpro.2024.100888
Josie A Christopher, Lisa M Breckels, Oliver M Crook, Mercedes Vazquez-Chantada, Derek Barratt, Kathryn S Lilley
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Abstract

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.

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整体蛋白质组学表明亚细胞特异性抗铁致凋亡反应电离辐射。
细胞对电离辐射(IR)的背景水平有许多保护机制,这些机制由表达、翻译后修饰和亚细胞定位的分子变化所协调。肿瘤学中的放射治疗试图克服这种机制,但放射耐药性是一个持续的挑战。在这里,全球亚细胞蛋白质组学结合贝叶斯模型在6gy x射线照射下鉴定出A549细胞中544种差异定位的蛋白质,揭示了与铁依赖性细胞死亡有关的蛋白质的亚细胞特异性变化,提示潜在的辐射抗性机制。这些观察结果与表达变化无关,强调了全局亚细胞蛋白质组学的实用性,以及抗辐射耐药诱导铁中毒疗法的前景。
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来源期刊
Molecular & Cellular Proteomics
Molecular & Cellular Proteomics 生物-生化研究方法
CiteScore
11.50
自引率
4.30%
发文量
131
审稿时长
84 days
期刊介绍: The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes
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