Claudio Mauro1,4, Shi Chi Leow1,2,4, Elena Anso3, et. al.
1 - Section of Inflammation and Signal Transduction, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
2 - Laboratory of NF-κB Signaling, Proteos, Singapore 138673, Singapore.
3 - Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
4 - These authors contributed equally to this work.
Published in Nature Cell Biology, 28 August 2011 (Epub ahead of print)
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). 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.