NF-kappa B 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

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    178 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1272-U234
    Number of pages18
    JournalNature Cell Biology
    Volume13
    Issue number10
    DOIs
    Publication statusPublished - Oct 2011

    Keywords

    • TNF-ALPHA
    • TUMOR-SUPPRESSOR
    • MOUSE MODEL
    • CELL-DEATH
    • P53
    • APOPTOSIS
    • CANCER
    • TRANSFORMATION
    • GROWTH
    • RAS

    Cite this

    Mauro, C., Leow, S. C., Anso, E., Rocha, S., Thotakura, A. K., Tornatore, L., Moretti, M., De Smaele, E., Beg, A. A., Tergaonkar, V., Chandel, N. S., & Franzoso, G. (2011). NF-kappa B controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration. Nature Cell Biology, 13(10), 1272-U234. https://doi.org/10.1038/ncb2324