ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging
Abstract Reactive thiols of proteinaceous cysteines are vital to cell biology by serving as sensor, effector and buffer of environmental redox fluctuations. Being the major source, as well as the prime target, of reactive oxygen species (ROS), mitochondria confront great challenges in preserving the...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60503-z |
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| _version_ | 1849469841515216896 |
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| author | Fengli Xu Haipeng Huang Kun Peng Chongshu Jian Hao Wu Zhiwen Jing Shan Qiu Ying Chen Keke Liu Ling Fu Yanru Wang Jing Yang Xiaotao Duan Chu Wang Heping Cheng Xianhua Wang |
| author_facet | Fengli Xu Haipeng Huang Kun Peng Chongshu Jian Hao Wu Zhiwen Jing Shan Qiu Ying Chen Keke Liu Ling Fu Yanru Wang Jing Yang Xiaotao Duan Chu Wang Heping Cheng Xianhua Wang |
| author_sort | Fengli Xu |
| collection | DOAJ |
| description | Abstract Reactive thiols of proteinaceous cysteines are vital to cell biology by serving as sensor, effector and buffer of environmental redox fluctuations. Being the major source, as well as the prime target, of reactive oxygen species (ROS), mitochondria confront great challenges in preserving their thiol pool. Here we show that ROS modulator 1 (ROMO1), a small inner mitochondrial membrane protein, plays a role in protecting the mitochondrial cysteinome. ROMO1 is redox sensitive and reactive and overexpression can prevent deleterious oxidation of proteinaceous thiols. ROMO1 upregulation leads to a reductive shift of the mitochondrial cysteinome, exerting beneficial effects on mitochondria, such as promoting energy metabolism and Ca2+ uniport while inhibiting vicious membrane permeability transition. Importantly, ROMO1 overexpression reverses mitochondrial cysteinome oxidations in multiple organs and slows functional decline in aged male mice. These findings unravel a redox regulatory mechanism of the mitochondrial cysteinome and mark ROMO1 as a potential target for combating oxidative stress and improving healthspan. |
| format | Article |
| id | doaj-art-500f6842c9694cd89e8a9ff365444afa |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-500f6842c9694cd89e8a9ff365444afa2025-08-20T03:25:19ZengNature PortfolioNature Communications2041-17232025-06-0116112010.1038/s41467-025-60503-zROMO1 overexpression protects the mitochondrial cysteinome from oxidations in agingFengli Xu0Haipeng Huang1Kun Peng2Chongshu Jian3Hao Wu4Zhiwen Jing5Shan Qiu6Ying Chen7Keke Liu8Ling Fu9Yanru Wang10Jing Yang11Xiaotao Duan12Chu Wang13Heping Cheng14Xianhua Wang15State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversitySynthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking UniversityNational Center for Protein Sciences-Beijing, Beijing Institute of LifeomicsNational Center for Protein Sciences-Beijing, Beijing Institute of LifeomicsState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityNational Center for Protein Sciences-Beijing, Beijing Institute of LifeomicsState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyPeking-Tsinghua Center for Life Sciences, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityState Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking UniversityAbstract Reactive thiols of proteinaceous cysteines are vital to cell biology by serving as sensor, effector and buffer of environmental redox fluctuations. Being the major source, as well as the prime target, of reactive oxygen species (ROS), mitochondria confront great challenges in preserving their thiol pool. Here we show that ROS modulator 1 (ROMO1), a small inner mitochondrial membrane protein, plays a role in protecting the mitochondrial cysteinome. ROMO1 is redox sensitive and reactive and overexpression can prevent deleterious oxidation of proteinaceous thiols. ROMO1 upregulation leads to a reductive shift of the mitochondrial cysteinome, exerting beneficial effects on mitochondria, such as promoting energy metabolism and Ca2+ uniport while inhibiting vicious membrane permeability transition. Importantly, ROMO1 overexpression reverses mitochondrial cysteinome oxidations in multiple organs and slows functional decline in aged male mice. These findings unravel a redox regulatory mechanism of the mitochondrial cysteinome and mark ROMO1 as a potential target for combating oxidative stress and improving healthspan.https://doi.org/10.1038/s41467-025-60503-z |
| spellingShingle | Fengli Xu Haipeng Huang Kun Peng Chongshu Jian Hao Wu Zhiwen Jing Shan Qiu Ying Chen Keke Liu Ling Fu Yanru Wang Jing Yang Xiaotao Duan Chu Wang Heping Cheng Xianhua Wang ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging Nature Communications |
| title | ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging |
| title_full | ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging |
| title_fullStr | ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging |
| title_full_unstemmed | ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging |
| title_short | ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging |
| title_sort | romo1 overexpression protects the mitochondrial cysteinome from oxidations in aging |
| url | https://doi.org/10.1038/s41467-025-60503-z |
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