Loss of heat shock factor initiates intracellular lipid surveillance by actin destabilization

Abigail Watterson, Sonja L.B. Arneaud, Naureen Wajahat, Jordan M. Wall, Lexus Tatge, Shaghayegh T. Beheshti, Melina Mihelakis, Nicholas Y. Cheatwood, Jacob McClendon, Atossa Ghorashi, Ishmael Dehghan, Chase D. Corley, Jeffrey G. McDonald, Peter M. Douglas

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Cells sense stress and initiate response pathways to maintain lipid and protein homeostasis. However, the interplay between these adaptive mechanisms is unclear. Herein, we demonstrate how imbalances in cytosolic protein homeostasis affect intracellular lipid surveillance. Independent of its ancient thermo-protective properties, the heat shock factor, HSF-1, modulates lipid metabolism and age regulation through the metazoan-specific nuclear hormone receptor, NHR-49. Reduced hsf-1 expression destabilizes the Caenorhabditis elegans enteric actin network, subsequently disrupting Rab GTPase-mediated trafficking and cell-surface residency of nutrient transporters. The ensuing malabsorption limits lipid availability, thereby activating the intracellular lipid surveillance response through vesicular release and nuclear translocation of NHR-49 to both increase nutrient absorption and restore lipid homeostasis. Overall, cooperation between these regulators of cytosolic protein homeostasis and lipid surveillance ensures metabolic health and age progression through actin integrity, endocytic recycling, and lipid sensing.

Original languageEnglish (US)
Article number111493
JournalCell Reports
Volume41
Issue number3
DOIs
StatePublished - Oct 18 2022

Keywords

  • CP: Cell biology
  • NHR-49
  • Rab GTPase
  • absorption
  • actin cytoskeleton
  • geranylgeranylation
  • heat shock factor
  • lipid sensing
  • lipid surveillance
  • nuclear hormone receptor
  • protein homeostasis

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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