Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development
Succinylation represents an emerging class of post-translational modifications (PTMs), characterized by the enzymatic or non-enzymatic transfer of a negatively charged four-carbon succinyl group to the ϵ-amino group of lysine residues, mediated by succinyl-coenzyme A. Recent studies have highlighted...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531246/full |
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| author | Zhangmin Ke Zhangmin Ke Kaikai Shen Li Wang Hao Xu Xia Pan Zhenjue Qian Yuting Wen Tangfeng Lv Xiuwei Zhang Yong Song |
| author_facet | Zhangmin Ke Zhangmin Ke Kaikai Shen Li Wang Hao Xu Xia Pan Zhenjue Qian Yuting Wen Tangfeng Lv Xiuwei Zhang Yong Song |
| author_sort | Zhangmin Ke |
| collection | DOAJ |
| description | Succinylation represents an emerging class of post-translational modifications (PTMs), characterized by the enzymatic or non-enzymatic transfer of a negatively charged four-carbon succinyl group to the ϵ-amino group of lysine residues, mediated by succinyl-coenzyme A. Recent studies have highlighted the involvement of succinylation in various diseases, particularly cancer progression. Sirtuin 5 (SIRT5), a member of the sirtuin family, has been extensively studied for its robust desuccinylase activity, alongside its deacetylase function. To date, only a limited number of SIRT5 substrates have been identified. These substrates mediate diverse physiological processes such as glucose oxidation, fatty acid oxidation, ammonia detoxification, reactive oxygen species scavenging, anti-apoptosis, and inflammatory responses. The regulation of these activities can occur through either the same enzymatic activity acting on different substrates or distinct enzymatic activities targeting the same substrate. Aberrant expression of SIRT5 has been closely linked to tumorigenesis and disease progression; however, its role remains controversial. SIRT5 exhibits dual functionalities: it can promote tumor proliferation, metastasis, drug resistance, and metabolic reprogramming, thereby acting as an oncogene; conversely, it can also inhibit tumor cell growth and induce apoptosis, functioning as a tumor suppressor gene. This review aims to provide a comprehensive overview of the current research status of SIRT5. We discuss its structural characteristics and regulatory mechanisms, compare its functions with other sirtuin family members, and elucidate the mechanisms regulating SIRT5 activity. Specifically, we focus on the role of succinylation modification mediated by SIRT5 in tumor progression, highlighting how desuccinylation by SIRT5 modulates tumor development and delineating the underlying mechanisms involved. |
| format | Article |
| id | doaj-art-ea0c544cb9f94e62a76c278ac3c2d90c |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ea0c544cb9f94e62a76c278ac3c2d90c2025-01-29T06:45:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15312461531246Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer developmentZhangmin Ke0Zhangmin Ke1Kaikai Shen2Li Wang3Hao Xu4Xia Pan5Zhenjue Qian6Yuting Wen7Tangfeng Lv8Xiuwei Zhang9Yong Song10Department of Respiratory and Critical Care Medicine, Affiliated Jiangning Hospital of Nanjing Medicine University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Jiangning Hospital of Nanjing Medicine University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Jiangning Hospital of Nanjing Medicine University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Jiangning Hospital of Nanjing Medicine University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Jiangning Hospital of Nanjing Medicine University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Jiangning Hospital of Nanjing Medicine University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, ChinaSuccinylation represents an emerging class of post-translational modifications (PTMs), characterized by the enzymatic or non-enzymatic transfer of a negatively charged four-carbon succinyl group to the ϵ-amino group of lysine residues, mediated by succinyl-coenzyme A. Recent studies have highlighted the involvement of succinylation in various diseases, particularly cancer progression. Sirtuin 5 (SIRT5), a member of the sirtuin family, has been extensively studied for its robust desuccinylase activity, alongside its deacetylase function. To date, only a limited number of SIRT5 substrates have been identified. These substrates mediate diverse physiological processes such as glucose oxidation, fatty acid oxidation, ammonia detoxification, reactive oxygen species scavenging, anti-apoptosis, and inflammatory responses. The regulation of these activities can occur through either the same enzymatic activity acting on different substrates or distinct enzymatic activities targeting the same substrate. Aberrant expression of SIRT5 has been closely linked to tumorigenesis and disease progression; however, its role remains controversial. SIRT5 exhibits dual functionalities: it can promote tumor proliferation, metastasis, drug resistance, and metabolic reprogramming, thereby acting as an oncogene; conversely, it can also inhibit tumor cell growth and induce apoptosis, functioning as a tumor suppressor gene. This review aims to provide a comprehensive overview of the current research status of SIRT5. We discuss its structural characteristics and regulatory mechanisms, compare its functions with other sirtuin family members, and elucidate the mechanisms regulating SIRT5 activity. Specifically, we focus on the role of succinylation modification mediated by SIRT5 in tumor progression, highlighting how desuccinylation by SIRT5 modulates tumor development and delineating the underlying mechanisms involved.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531246/fullSIRT5cancersuccinylationdesuccinylasesirtuin |
| spellingShingle | Zhangmin Ke Zhangmin Ke Kaikai Shen Li Wang Hao Xu Xia Pan Zhenjue Qian Yuting Wen Tangfeng Lv Xiuwei Zhang Yong Song Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development Frontiers in Immunology SIRT5 cancer succinylation desuccinylase sirtuin |
| title | Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development |
| title_full | Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development |
| title_fullStr | Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development |
| title_full_unstemmed | Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development |
| title_short | Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development |
| title_sort | emerging roles of mitochondrial sirtuin sirt5 in succinylation modification and cancer development |
| topic | SIRT5 cancer succinylation desuccinylase sirtuin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531246/full |
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