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bioRxiv · 10.1101/2024.09.12.611851

Global proteomics indicates subcellular-specific anti-ferroptotic responses to ionizing radiation

Christopher, J. A.·Breckels, L. M.·Crook, O. M.·Vazquez-Chantada, M.·Barratt, D.·Lilley, K. S.
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Abstract

Cells have many protective mechanisms against background levels of ionizing radiation (IR) orchestrated by molecular changes in expression, post-translation modifications and subcellular localization. Radiotherapeutic treatment in oncology attempts to overwhelm such mechanisms, but radio-resistance is an ongoing challenge. Here, global subcellular proteomics combined with Bayesian modelling 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 radio-resistance mechanisms. These observations were independent of expression changes, emphasizing the utility of global subcellular proteomics and the promising prospect of ferroptosis-inducing therapies for combatting radioresistance.

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Christopher, J. A., Breckels, L. M., Crook, O. M., Vazquez-Chantada, M., Barratt, D., Lilley, K. S.. 2024-09-12. Global proteomics indicates subcellular-specific anti-ferroptotic responses to ionizing radiation. https://doi.org/10.1101/2024.09.12.611851

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