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SREBP modulates the NADP+/NADPH cycle to control night sleep in Drosophila

Author

Listed:
  • Vittoria Mariano

    (University of Lausanne
    KU Leuven)

  • Alexandros K. Kanellopoulos

    (University of Lausanne)

  • Giuseppe Aiello

    (University of Lausanne)

  • Adrian C. Lo

    (University of Lausanne)

  • Eric Legius

    (KU Leuven)

  • Tilmann Achsel

    (University of Lausanne)

  • Claudia Bagni

    (University of Lausanne
    University of Rome “Tor Vergata”)

Abstract

Sleep behavior is conserved throughout evolution, and sleep disturbances are a frequent comorbidity of neuropsychiatric disorders. However, the molecular basis underlying sleep dysfunctions in neurological diseases remains elusive. Using a model for neurodevelopmental disorders (NDDs), the Drosophila Cytoplasmic FMR1 interacting protein haploinsufficiency (Cyfip85.1/+), we identify a mechanism modulating sleep homeostasis. We show that increased activity of the sterol regulatory element-binding protein (SREBP) in Cyfip85.1/+ flies induces an increase in the transcription of wakefulness-associated genes, such as the malic enzyme (Men), causing a disturbance in the daily NADP+/NADPH ratio oscillations and reducing sleep pressure at the night-time onset. Reduction in SREBP or Men activity in Cyfip85.1/+ flies enhances the NADP+/NADPH ratio and rescues the sleep deficits, indicating that SREBP and Men are causative for the sleep deficits in Cyfip heterozygous flies. This work suggests modulation of the SREBP metabolic axis as a new avenue worth exploring for its therapeutic potential in sleep disorders.

Suggested Citation

  • Vittoria Mariano & Alexandros K. Kanellopoulos & Giuseppe Aiello & Adrian C. Lo & Eric Legius & Tilmann Achsel & Claudia Bagni, 2023. "SREBP modulates the NADP+/NADPH cycle to control night sleep in Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35577-8
    DOI: 10.1038/s41467-022-35577-8
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    References listed on IDEAS

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    1. Nuria Domínguez-Iturza & Adrian C. Lo & Disha Shah & Marcelo Armendáriz & Anna Vannelli & Valentina Mercaldo & Massimo Trusel & Ka Wan Li & Denise Gastaldo & Ana Rita Santos & Zsuzsanna Callaerts-Vegh, 2019. "The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Chiara Cirelli & Daniel Bushey & Sean Hill & Reto Huber & Robert Kreber & Barry Ganetzky & Giulio Tononi, 2005. "Reduced sleep in Drosophila Shaker mutants," Nature, Nature, vol. 434(7037), pages 1087-1092, April.
    3. Shaun M. Purcell & Jennifer L. Moran & Menachem Fromer & Douglas Ruderfer & Nadia Solovieff & Panos Roussos & Colm O’Dushlaine & Kimberly Chambert & Sarah E. Bergen & Anna Kähler & Laramie Duncan & El, 2014. "A polygenic burden of rare disruptive mutations in schizophrenia," Nature, Nature, vol. 506(7487), pages 185-190, February.
    4. Hreinn Stefansson & Dan Rujescu & Sven Cichon & Olli P. H. Pietiläinen & Andres Ingason & Stacy Steinberg & Ragnheidur Fossdal & Engilbert Sigurdsson & Thordur Sigmundsson & Jacobine E. Buizer-Voskamp, 2008. "Large recurrent microdeletions associated with schizophrenia," Nature, Nature, vol. 455(7210), pages 232-236, September.
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