Work

FAT-5/SCD5-mediated lipid localization in lysosomes alleviates gamma radiation injury in Caenorhabditis elegans

Year: 2025

Type: article

Abstract: Accidental internal or external exposure to gamma radiation can cause severe injury to the human body. The identification of an effective medication target has become particularly important for the treatment of radiation-induced injury. In this work, Caenorhabditis elegans was found to tolerate high-dose radiation when exposed to an extremely low-temperature environment (at 4 °C) for 4 h before irradiation. Experimental confirmation revealed that metabolites excreted by C. elegans targeted the guanylyl cyclase GCY-5. Furthermore, GCY-5 activation by the excreted metabolites both suppressed lysosome acidification and promoted lipid translocation in lysosomes via FAT-5/SCD5. This ultimately resulted in the mitigation of radiation-induced damage. The pathway discovered in C. elegans was also confirmed in 293T cells, indicating a potential new target for radiation-induced damage research. A radiotherapy prognosis analysis based on the TCGA database indicated that assessing SCD5 expression in patients with kidney renal clear cell carcinoma (KIRC) during clinical treatment may aid in evaluating their suitability for radiotherapy. This study provides clinicians with a valuable basis for developing more effective therapeutic strategies and an experimental basis for future investigations in this area.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.110674

Authors: Tong Zhu, Zhouxuan Wang, Jiaze Li, Yu Zhao, Saijun Fan

Institution: Chinese Academy of Medical Sciences & Peking Union Medical College

Language: English

Topic: Effects of Radiation Exposure

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430