NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration.
NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration.
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DOI：
10.1038/ncb2324
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发表时间：
2011-08-28
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞增殖是一个代谢要求很高的过程。它需要对细胞生物能途径进行主动重编程，以支持葡萄糖代谢的合成代谢生长。NF-κB/Rel转录因子在免疫、炎症和肿瘤发生过程中协调许多驱动增殖的信号，但NF-κB是否调节这些过程中细胞分裂所需的代谢重编程尚不清楚。在这里，我们报告NF-κB通过控制糖酵解和线粒体呼吸利用之间的平衡来组织能量代谢网络。NF-κB抑制在基础条件下导致细胞重编程为有氧糖酵解，并在葡萄糖饥饿时诱导坏死。NF-κB抑制导致的代谢重组克服了致癌转化中肿瘤抑制突变的要求，并损害了体内癌症的代谢适应。这种NF-κ B依赖性代谢途径涉及通过上调细胞色素c氧化酶2（SCO 2;参考文献）的线粒体合成来刺激氧化磷酸化。我们的研究结果确定NF-κB作为线粒体呼吸的生理调节因子，并建立了NF-κB在正常细胞和癌症中代谢适应的作用。
Cell proliferation is a metabolically demanding process. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth. NF-κB/Rel transcription factors coordinate many of the signals that drive proliferation during Immunity, inflammation and oncogenesis, but whether NF-κB regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-κB organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-κB inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-κB inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-κB-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref.). Our findings identify NF-κB as a physiological regulator of mitochondrial respiration and establish a role for NF-κB in metabolic adaptation in normal cells and cancer.
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影响因子：
10.5
作者：
Guo, Jessie Yanxiang;Chen, Hsin-Yi;White, Eileen
通讯作者：
White, Eileen
影响因子：
21.3
作者：
Kawauchi, Keiko;Araki, Keigo;Tanaka, Nobuyuki
通讯作者：
Tanaka, Nobuyuki
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Pham, CG;Bubici, C;Franzoso, G
通讯作者：
Franzoso, G