NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1272-1279
Number of pages8
JournalNature Cell Biology
Volume13
Issue number10
DOIs
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration'. Together they form a unique fingerprint.

Cite this