Advances in the regulatory mechanisms of mTOR in necroptosis
The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1297408/full |
| _version_ | 1797387758110507008 |
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| author | Yawen Xie Guoyu Zhao Xianli Lei Na Cui Hao Wang |
| author_facet | Yawen Xie Guoyu Zhao Xianli Lei Na Cui Hao Wang |
| author_sort | Yawen Xie |
| collection | DOAJ |
| description | The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis. |
| first_indexed | 2024-03-08T22:29:44Z |
| format | Article |
| id | doaj.art-c768554c862d45c9b021c267ceeda529 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T22:29:44Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c768554c862d45c9b021c267ceeda5292023-12-18T06:55:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12974081297408Advances in the regulatory mechanisms of mTOR in necroptosisYawen Xie0Guoyu Zhao1Xianli Lei2Na Cui3Hao Wang4Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Critical Care Medicine, Beijing Jishuitan Hospital, Capital Medical University, Beijing, ChinaThe mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1297408/fullmTORnecroptosisautophagyRIPKROS |
| spellingShingle | Yawen Xie Guoyu Zhao Xianli Lei Na Cui Hao Wang Advances in the regulatory mechanisms of mTOR in necroptosis Frontiers in Immunology mTOR necroptosis autophagy RIPK ROS |
| title | Advances in the regulatory mechanisms of mTOR in necroptosis |
| title_full | Advances in the regulatory mechanisms of mTOR in necroptosis |
| title_fullStr | Advances in the regulatory mechanisms of mTOR in necroptosis |
| title_full_unstemmed | Advances in the regulatory mechanisms of mTOR in necroptosis |
| title_short | Advances in the regulatory mechanisms of mTOR in necroptosis |
| title_sort | advances in the regulatory mechanisms of mtor in necroptosis |
| topic | mTOR necroptosis autophagy RIPK ROS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1297408/full |
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