Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation
Oxidative stress serves as a fundamental mechanism contributing to ionizing radiation-induced damage, which has significant implications for tissue injury. Cysteine dioxygenase type 1 (CDO1) catalyzes the rate-limiting step for cysteine oxidation pathway, thereby playing a crucial role in regulating...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725001697 |
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| author | Yumin He Dan Li Hongping Ye Jiang Zhu Qianming Chen Rui Liu |
| author_facet | Yumin He Dan Li Hongping Ye Jiang Zhu Qianming Chen Rui Liu |
| author_sort | Yumin He |
| collection | DOAJ |
| description | Oxidative stress serves as a fundamental mechanism contributing to ionizing radiation-induced damage, which has significant implications for tissue injury. Cysteine dioxygenase type 1 (CDO1) catalyzes the rate-limiting step for cysteine oxidation pathway, thereby playing a crucial role in regulating cellular cysteine availability. However, the regulation of CDO1 activity and cysteine oxidation under ionizing radiation, as well as their subsequent effects on cell viability, remains largely unexplored. In this study, we provide evidence that CDO1 activity and cysteine oxidation are inhibited following radiation exposure. Mechanistically, ionizing radiation-induced oxidative stress triggers glutathionylation of CDO1 at cysteine (C) 164, which impairs CDO1 enzymatic activity by disrupting its interaction with the substrate cysteine. Furthermore, glutathionylation at CDO1 C164 is essential for maintaining cellular redox homeostasis and supports cell viability under ionizing radiation. These findings reveal a novel mechanism through which redox modifications of CDO1 regulate cysteine metabolism and glutathione synthesis under oxidative stress, thereby underscoring its potential as a therapeutic target for addressing radiation-induced injuries. |
| format | Article |
| id | doaj-art-09a2b21a560e46b3af2d8e9b77d8ccf1 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-09a2b21a560e46b3af2d8e9b77d8ccf12025-08-20T03:49:41ZengElsevierRedox Biology2213-23172025-06-018310365610.1016/j.redox.2025.103656Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiationYumin He0Dan Li1Hongping Ye2Jiang Zhu3Qianming Chen4Rui Liu5State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaDepartment of Urology, Xindu District People's Hospital of Chengdu, Chengdu, 610500, PR China; Corresponding author.State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, PR China; Corresponding author.State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, PR China; Corresponding author.Oxidative stress serves as a fundamental mechanism contributing to ionizing radiation-induced damage, which has significant implications for tissue injury. Cysteine dioxygenase type 1 (CDO1) catalyzes the rate-limiting step for cysteine oxidation pathway, thereby playing a crucial role in regulating cellular cysteine availability. However, the regulation of CDO1 activity and cysteine oxidation under ionizing radiation, as well as their subsequent effects on cell viability, remains largely unexplored. In this study, we provide evidence that CDO1 activity and cysteine oxidation are inhibited following radiation exposure. Mechanistically, ionizing radiation-induced oxidative stress triggers glutathionylation of CDO1 at cysteine (C) 164, which impairs CDO1 enzymatic activity by disrupting its interaction with the substrate cysteine. Furthermore, glutathionylation at CDO1 C164 is essential for maintaining cellular redox homeostasis and supports cell viability under ionizing radiation. These findings reveal a novel mechanism through which redox modifications of CDO1 regulate cysteine metabolism and glutathione synthesis under oxidative stress, thereby underscoring its potential as a therapeutic target for addressing radiation-induced injuries.http://www.sciencedirect.com/science/article/pii/S2213231725001697CDO1GlutathionylationOxidative stressRadiation damageCysteine metabolism |
| spellingShingle | Yumin He Dan Li Hongping Ye Jiang Zhu Qianming Chen Rui Liu Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation Redox Biology CDO1 Glutathionylation Oxidative stress Radiation damage Cysteine metabolism |
| title | Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation |
| title_full | Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation |
| title_fullStr | Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation |
| title_full_unstemmed | Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation |
| title_short | Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation |
| title_sort | oxidative stress induced cdo1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation |
| topic | CDO1 Glutathionylation Oxidative stress Radiation damage Cysteine metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725001697 |
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