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

    Research output: Contribution to journalArticle

    160 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., ... 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
    Mauro, Claudio ; Leow, Shi Chi ; Anso, Elena ; Rocha, Sonia ; Thotakura, Anil K. ; Tornatore, Laura ; Moretti, Marta ; De Smaele, Enrico ; Beg, Amer A. ; Tergaonkar, Vinay ; Chandel, Navdeep S. ; Franzoso, Guido. / NF-kappa B controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration. In: Nature Cell Biology. 2011 ; Vol. 13, No. 10. pp. 1272-U234.
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    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.",
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    author = "Claudio Mauro and Leow, {Shi Chi} and Elena Anso and Sonia Rocha and Thotakura, {Anil K.} and Laura Tornatore and Marta Moretti and {De Smaele}, Enrico and Beg, {Amer A.} and Vinay Tergaonkar and Chandel, {Navdeep S.} and Guido Franzoso",
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    Mauro, C, Leow, SC, Anso, E, Rocha, S, Thotakura, AK, Tornatore, L, Moretti, M, De Smaele, E, Beg, AA, Tergaonkar, V, Chandel, NS & Franzoso, G 2011, 'NF-kappa B controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration', Nature Cell Biology, vol. 13, no. 10, pp. 1272-U234. https://doi.org/10.1038/ncb2324

    NF-kappa B controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration. / Mauro, Claudio; Leow, Shi Chi; Anso, Elena; Rocha, Sonia; Thotakura, Anil K.; Tornatore, Laura; Moretti, Marta; De Smaele, Enrico; Beg, Amer A.; Tergaonkar, Vinay; Chandel, Navdeep S.; Franzoso, Guido.

    In: Nature Cell Biology, Vol. 13, No. 10, 10.2011, p. 1272-U234.

    Research output: Contribution to journalArticle

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    AU - Mauro, Claudio

    AU - Leow, Shi Chi

    AU - Anso, Elena

    AU - Rocha, Sonia

    AU - Thotakura, Anil K.

    AU - Tornatore, Laura

    AU - Moretti, Marta

    AU - De Smaele, Enrico

    AU - Beg, Amer A.

    AU - Tergaonkar, Vinay

    AU - Chandel, Navdeep S.

    AU - Franzoso, Guido

    PY - 2011/10

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    N2 - 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.

    AB - 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.

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    KW - TUMOR-SUPPRESSOR

    KW - MOUSE MODEL

    KW - CELL-DEATH

    KW - P53

    KW - APOPTOSIS

    KW - CANCER

    KW - TRANSFORMATION

    KW - GROWTH

    KW - RAS

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    DO - 10.1038/ncb2324

    M3 - Article

    VL - 13

    SP - 1272-U234

    JO - Nature Cell Biology

    JF - Nature Cell Biology

    SN - 1465-7392

    IS - 10

    ER -