The dual role of PGAM5 in inflammation
Abstract In recent years, the focus on human inflammation in research has increased, with aging-related inflammation widely recognized as a defining characteristic of aging. Inflammation is strongly correlated with mitochondrial dysfunction. Phosphoglycerate mutase family member 5 (PGAM5) is a novel...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-025-01391-7 |
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| author | Yuxin Qi Bhavana Rajbanshi Ruihan Hao Yifan Dang Churong Xu Wei Lu Liming Dai Bingjun Zhang Xiaoling Zhang |
| author_facet | Yuxin Qi Bhavana Rajbanshi Ruihan Hao Yifan Dang Churong Xu Wei Lu Liming Dai Bingjun Zhang Xiaoling Zhang |
| author_sort | Yuxin Qi |
| collection | DOAJ |
| description | Abstract In recent years, the focus on human inflammation in research has increased, with aging-related inflammation widely recognized as a defining characteristic of aging. Inflammation is strongly correlated with mitochondrial dysfunction. Phosphoglycerate mutase family member 5 (PGAM5) is a novel modulator of mitochondrial homeostasis in response to mechanical stimulation. Here we review the structure and sublocalization of PGAM5, introduce its importance in programmed cell death and summarize its crucial roles in the development and progression of inflammatory diseases such as pneumonia, hepatitis, neuroinflammation and aging. Notably, PGAM5 has dual effects on controlling inflammation: distinct PGAM5-mediated mitochondrial functions exhibit cellular heterogeneity, leading to its dual functions in inflammation control. We therefore highlight the double-edged sword nature of PGAM5 as a potential critical regulator and innovative therapeutic target in inflammation. Finally, the challenges and future directions of the use of PGAM5, which has dual properties, as a target molecule in the clinic are discussed. This review provides crucial insights to guide the development of intelligent therapeutic strategies targeting PGAM5-specific regulation to treat intractable inflammatory conditions, as well as the potential extension of its broader application to other diseases to achieve more precise and effective treatment outcomes. |
| format | Article |
| id | doaj-art-bb863ad5db344530bb608913d7fb351b |
| institution | DOAJ |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-bb863ad5db344530bb608913d7fb351b2025-08-20T03:05:57ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-02-0157229831110.1038/s12276-025-01391-7The dual role of PGAM5 in inflammationYuxin Qi0Bhavana Rajbanshi1Ruihan Hao2Yifan Dang3Churong Xu4Wei Lu5Liming Dai6Bingjun Zhang7Xiaoling Zhang8Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Dermatology and Venereology, Tongji University School of MedicineDepartment of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Facility for Translational MedicineCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesDepartment of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineAbstract In recent years, the focus on human inflammation in research has increased, with aging-related inflammation widely recognized as a defining characteristic of aging. Inflammation is strongly correlated with mitochondrial dysfunction. Phosphoglycerate mutase family member 5 (PGAM5) is a novel modulator of mitochondrial homeostasis in response to mechanical stimulation. Here we review the structure and sublocalization of PGAM5, introduce its importance in programmed cell death and summarize its crucial roles in the development and progression of inflammatory diseases such as pneumonia, hepatitis, neuroinflammation and aging. Notably, PGAM5 has dual effects on controlling inflammation: distinct PGAM5-mediated mitochondrial functions exhibit cellular heterogeneity, leading to its dual functions in inflammation control. We therefore highlight the double-edged sword nature of PGAM5 as a potential critical regulator and innovative therapeutic target in inflammation. Finally, the challenges and future directions of the use of PGAM5, which has dual properties, as a target molecule in the clinic are discussed. This review provides crucial insights to guide the development of intelligent therapeutic strategies targeting PGAM5-specific regulation to treat intractable inflammatory conditions, as well as the potential extension of its broader application to other diseases to achieve more precise and effective treatment outcomes.https://doi.org/10.1038/s12276-025-01391-7 |
| spellingShingle | Yuxin Qi Bhavana Rajbanshi Ruihan Hao Yifan Dang Churong Xu Wei Lu Liming Dai Bingjun Zhang Xiaoling Zhang The dual role of PGAM5 in inflammation Experimental and Molecular Medicine |
| title | The dual role of PGAM5 in inflammation |
| title_full | The dual role of PGAM5 in inflammation |
| title_fullStr | The dual role of PGAM5 in inflammation |
| title_full_unstemmed | The dual role of PGAM5 in inflammation |
| title_short | The dual role of PGAM5 in inflammation |
| title_sort | dual role of pgam5 in inflammation |
| url | https://doi.org/10.1038/s12276-025-01391-7 |
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