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Intracellular lipid surveillance by small G protein geranylgeranylation

Author

Listed:
  • Abigail Watterson

    (University of Texas Southwestern Medical Center)

  • Lexus Tatge

    (University of Texas Southwestern Medical Center)

  • Naureen Wajahat

    (University of Texas Southwestern Medical Center
    University of Texas at Dallas)

  • Sonja L. B. Arneaud

    (University of Texas Southwestern Medical Center)

  • Rene Solano Fonseca

    (University of Texas Southwestern Medical Center)

  • Shaghayegh T. Beheshti

    (University of Texas Southwestern Medical Center
    University of Texas at Dallas)

  • Patrick Metang

    (University of Texas Southwestern Medical Center)

  • Melina Mihelakis

    (University of Texas Southwestern Medical Center)

  • Kielen R. Zuurbier

    (University of Texas Southwestern Medical Center)

  • Chase D. Corley

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Ishmael Dehghan

    (University of Texas Southwestern Medical Center)

  • Jeffrey G. McDonald

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Peter M. Douglas

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

Abstract

Imbalances in lipid homeostasis can have deleterious effects on health1,2. Yet how cells sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption remains unclear. Here we describe a mechanism for intracellular lipid surveillance in Caenorhabditis elegans that involves transcriptional inactivation of the nuclear hormone receptor NHR-49 through its cytosolic sequestration to endocytic vesicles via geranylgeranyl conjugation to the small G protein RAB-11.1. Defective de novo isoprenoid synthesis caused by lipid depletion limits RAB-11.1 geranylgeranylation, which promotes nuclear translocation of NHR-49 and activation of rab-11.2 transcription to enhance transporter residency at the plasma membrane. Thus, we identify a critical lipid sensed by the cell, its conjugated G protein, and the nuclear receptor whose dynamic interactions enable cells to sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption and lipid metabolism.

Suggested Citation

  • Abigail Watterson & Lexus Tatge & Naureen Wajahat & Sonja L. B. Arneaud & Rene Solano Fonseca & Shaghayegh T. Beheshti & Patrick Metang & Melina Mihelakis & Kielen R. Zuurbier & Chase D. Corley & Ishm, 2022. "Intracellular lipid surveillance by small G protein geranylgeranylation," Nature, Nature, vol. 605(7911), pages 736-740, May.
    • Handle: RePEc:nat:nature:v:605:y:2022:i:7911:d:10.1038_s41586-022-04729-7
    DOI: 10.1038/s41586-022-04729-7
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    Cited by:

    1. Annmary Paul Erinjeri & Xunyan Wang & Rhianna Williams & Riccardo Zenezini Chiozzi & Konstantinos Thalassinos & Johnathan Labbadia, 2024. "HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Simona Pisanti & Erika Rimondi & Elena Pozza & Elisabetta Melloni & Enrico Zauli & Maurizio Bifulco & Rosanna Martinelli & Annalisa Marcuzzi, 2022. "Prenylation Defects and Oxidative Stress Trigger the Main Consequences of Neuroinflammation Linked to Mevalonate Pathway Deregulation," IJERPH, MDPI, vol. 19(15), pages 1-15, July.

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