NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration
Author: ["Claudio Mauro","Shi Chi Leow","Elena Anso","Sonia Rocha","Anil K. Thotakura","Laura Tornatore","Marta Moretti","Enrico De Smaele","Amer A. Beg","Vinay Tergaonkar","Navdeep S. Chandel","Guido Franzoso"]
Publication: Nature Cell Biology
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Abstract
Franzoso and colleagues show that NF-κB protects cells from nutrient-starvation-induced necrosis by upregulating mitochondrial respiration through increased p53-dependent expression of the SCO2 enzyme. Conversely, inhibition of NF-κB results in increased aerobic glycolysis, known as the Warburg effect, thus promoting oncogenic transformation, and affects metabolic adaptation during tumorigenesis in vivo. Cell proliferation is a metabolically demanding process1,2. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth1,2. NF-κB/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis3, 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. 4). 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.
Cite this article
Mauro, C., Leow, S., Anso, E. et al. NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration. Nat Cell Biol 13, 1272–1279 (2011). https://doi.org/10.1038/ncb2324
