ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivation
Glucose deprivation (GD), a common metabolic stress condition, has been recognized as a potent inducer of necroptotic cell death. Our previous findings suggested that the mitochondrial protein, Noxa, may be involved in mediating the release of mitochondrial DNA during GD-induced ZBP1-dependent necro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cell Death |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fceld.2024.1507960/full |
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| author | Sasiprapa Sonkaew Sasiprapa Sonkaew Ruwaida Rajna Yeon-Ji Park Jiong Yan Zhaoshan Liu Siriporn Jitkaew Zheng-Gang Liu Swati Choksi |
| author_facet | Sasiprapa Sonkaew Sasiprapa Sonkaew Ruwaida Rajna Yeon-Ji Park Jiong Yan Zhaoshan Liu Siriporn Jitkaew Zheng-Gang Liu Swati Choksi |
| author_sort | Sasiprapa Sonkaew |
| collection | DOAJ |
| description | Glucose deprivation (GD), a common metabolic stress condition, has been recognized as a potent inducer of necroptotic cell death. Our previous findings suggested that the mitochondrial protein, Noxa, may be involved in mediating the release of mitochondrial DNA during GD-induced ZBP1-dependent necroptotic pathway. However, the functional significance of Noxa in necroptosis under GD treatment remains unclear. Here, we investigated the role of Noxa in GD-induced necroptosis and the underlying molecular mechanisms governing its expression. We revealed that Noxa is required for the induction of necroptosis under GD. We also demonstrated that the upregulation of Noxa induced by GD is mediated by ATF4, a key transcription factor. These results provide insights into the regulatory mechanisms underlying Noxa dynamics during GD treatment and highlights its potential as a therapeutic target in cancer therapy and necroptosis-related diseases. |
| format | Article |
| id | doaj-art-e16668cd937844a594bcb2911bf146eb |
| institution | Kabale University |
| issn | 2813-5563 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell Death |
| spelling | doaj-art-e16668cd937844a594bcb2911bf146eb2025-01-20T07:20:12ZengFrontiers Media S.A.Frontiers in Cell Death2813-55632025-01-01310.3389/fceld.2024.15079601507960ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivationSasiprapa Sonkaew0Sasiprapa Sonkaew1Ruwaida Rajna2Yeon-Ji Park3Jiong Yan4Zhaoshan Liu5Siriporn Jitkaew6Zheng-Gang Liu7Swati Choksi8National Cancer Institute, National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, United StatesGraduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, ThailandNational Cancer Institute, National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, United StatesNational Cancer Institute, National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, United StatesNational Cancer Institute, National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, United StatesNational Cancer Institute, National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, United StatesChulalongkorn University, Department of Clinical Chemistry, Bangkok, ThailandNational Cancer Institute, National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, United StatesNational Cancer Institute, National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, United StatesGlucose deprivation (GD), a common metabolic stress condition, has been recognized as a potent inducer of necroptotic cell death. Our previous findings suggested that the mitochondrial protein, Noxa, may be involved in mediating the release of mitochondrial DNA during GD-induced ZBP1-dependent necroptotic pathway. However, the functional significance of Noxa in necroptosis under GD treatment remains unclear. Here, we investigated the role of Noxa in GD-induced necroptosis and the underlying molecular mechanisms governing its expression. We revealed that Noxa is required for the induction of necroptosis under GD. We also demonstrated that the upregulation of Noxa induced by GD is mediated by ATF4, a key transcription factor. These results provide insights into the regulatory mechanisms underlying Noxa dynamics during GD treatment and highlights its potential as a therapeutic target in cancer therapy and necroptosis-related diseases.https://www.frontiersin.org/articles/10.3389/fceld.2024.1507960/fullglucose deprivationNoxaATF4necroptosiscell death |
| spellingShingle | Sasiprapa Sonkaew Sasiprapa Sonkaew Ruwaida Rajna Yeon-Ji Park Jiong Yan Zhaoshan Liu Siriporn Jitkaew Zheng-Gang Liu Swati Choksi ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivation Frontiers in Cell Death glucose deprivation Noxa ATF4 necroptosis cell death |
| title | ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivation |
| title_full | ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivation |
| title_fullStr | ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivation |
| title_full_unstemmed | ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivation |
| title_short | ATF4-mediated expression of NOXA is critical for necroptosis driven by glucose deprivation |
| title_sort | atf4 mediated expression of noxa is critical for necroptosis driven by glucose deprivation |
| topic | glucose deprivation Noxa ATF4 necroptosis cell death |
| url | https://www.frontiersin.org/articles/10.3389/fceld.2024.1507960/full |
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