NF-?B controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration.

Cell proliferation is a metabolically demanding process. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth. NF-?B/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis, but whether NF-?B regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-?B organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-?B inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-?B inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-?B-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref. ). Our findings identify NF-?B as a physiological regulator of mitochondrial respiration and establish a role for NF-?B in metabolic adaptation in normal cells and cancer. [ABSTRACT FROM AUTHOR]