期刊
NATURE CELL BIOLOGY
卷 13, 期 10, 页码 1272-U234出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2324
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资金
- AIRC (Italy)
- A*STAR (Singapore)
- Pasteur Institute, Cenci Bolognetti Foundation (Italy)
- NIH [R01 CA084040, R01 CA098583, R01 CA123067]
- Cancer Research UK [C26587/A8839]
- Cancer Research UK [12918] Funding Source: researchfish
Cell proliferation is a metabolically demanding process(1,2). It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth(1,2). NF-kappa B/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis(3), but whether NF-kappa B regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-kappa B organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondria! respiration. NF-kappa B inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-kappa B inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-kappa B-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref. 4). Our findings identify NF-kappa B as a physiological regulator of mitochondrial respiration and establish a role for NF-kappa B in metabolic adaptation in normal cells and cancer.
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