Intracellular lipid surveillance by small G protein geranylgeranylation

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, Ishmael Dehghan, Jeffrey G. McDonald, Peter M. Douglas

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)736-740
Number of pages5
JournalNature
Volume605
Issue number7911
DOIs
StatePublished - May 26 2022

ASJC Scopus subject areas

  • General

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