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REPTOR and CREBRF encode key regulators of muscle energy metabolism

Author

Listed:
  • Pedro Saavedra

    (Blavatnik Institute, Harvard Medical School)

  • Phillip A. Dumesic

    (Dana-Farber Cancer Institute
    Blavatnik Institute, Harvard Medical School)

  • Yanhui Hu

    (Blavatnik Institute, Harvard Medical School)

  • Elizabeth Filine

    (Blavatnik Institute, Harvard Medical School)

  • Patrick Jouandin

    (Institut de Recherche en Cancérologie de Montpellier, INSERM)

  • Richard Binari

    (Blavatnik Institute, Harvard Medical School
    Howard Hughes Medical Institute)

  • Sarah E. Wilensky

    (Dana-Farber Cancer Institute)

  • Jonathan Rodiger

    (Blavatnik Institute, Harvard Medical School)

  • Haiyun Wang

    (Tongji University)

  • Weihang Chen

    (Blavatnik Institute, Harvard Medical School)

  • Ying Liu

    (Blavatnik Institute, Harvard Medical School)

  • Bruce M. Spiegelman

    (Dana-Farber Cancer Institute
    Blavatnik Institute, Harvard Medical School)

  • Norbert Perrimon

    (Blavatnik Institute, Harvard Medical School
    Howard Hughes Medical Institute)

Abstract

Metabolic flexibility of muscle tissue describes the adaptive capacity to use different energy substrates according to their availability. The disruption of this ability associates with metabolic disease. Here, using a Drosophila model of systemic metabolic dysfunction triggered by yorkie-induced gut tumors, we show that the transcription factor REPTOR is an important regulator of energy metabolism in muscles. We present evidence that REPTOR is activated in muscles of adult flies with gut yorkie-tumors, where it modulates glucose metabolism. Further, in vivo studies indicate that sustained activity of REPTOR is sufficient in wildtype muscles to repress glycolysis and increase tricarboxylic acid (TCA) cycle metabolites. Consistent with the fly studies, higher levels of CREBRF, the mammalian ortholog of REPTOR, reduce glycolysis in mouse myotubes while promoting oxidative metabolism. Altogether, our results define a conserved function for REPTOR and CREBRF as key regulators of muscle energy metabolism.

Suggested Citation

  • Pedro Saavedra & Phillip A. Dumesic & Yanhui Hu & Elizabeth Filine & Patrick Jouandin & Richard Binari & Sarah E. Wilensky & Jonathan Rodiger & Haiyun Wang & Weihang Chen & Ying Liu & Bruce M. Spiegel, 2023. "REPTOR and CREBRF encode key regulators of muscle energy metabolism," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40595-1
    DOI: 10.1038/s41467-023-40595-1
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