Sonkaew Sasiprapa, Rajna Ruwaida, Park Yeon-Ji, Yan Jiong, Liu Zhaoshan, Jitkaew Siriporn, Liu Zheng-Gang, Choksi Swati
National Cancer Institute; National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, USA.
Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Front Cell Death. 2025;3. doi: 10.3389/fceld.2024.1507960. Epub 2025 Jan 20.
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.
葡萄糖剥夺（GD）是一种常见的代谢应激状况，已被公认为坏死性凋亡细胞死亡的强效诱导剂。我们之前的研究结果表明，线粒体蛋白Noxa可能参与介导葡萄糖剥夺诱导的ZBP1依赖性坏死性凋亡途径中线粒体DNA的释放。然而，在葡萄糖剥夺处理下，Noxa在坏死性凋亡中的功能意义仍不清楚。在此，我们研究了Noxa在葡萄糖剥夺诱导的坏死性凋亡中的作用以及调控其表达的潜在分子机制。我们发现，葡萄糖剥夺诱导坏死性凋亡需要Noxa。我们还证明，葡萄糖剥夺诱导的Noxa上调是由关键转录因子ATF4介导的。这些结果为葡萄糖剥夺处理期间Noxa动态变化的调控机制提供了见解，并突出了其作为癌症治疗和坏死性凋亡相关疾病治疗靶点的潜力。
