1. Loss of heat shock factor initiates intracellular lipid surveillance by actin destabilization.
- Author
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Watterson A, Arneaud SLB, Wajahat N, Wall JM, Tatge L, Beheshti ST, Mihelakis M, Cheatwood NY, McClendon J, Ghorashi A, Dehghan I, Corley CD, McDonald JG, and Douglas PM
- Subjects
- Animals, Actins metabolism, Caenorhabditis elegans metabolism, Heat-Shock Response, Transcription Factors metabolism, Receptors, Cytoplasmic and Nuclear metabolism, Lipids, rab GTP-Binding Proteins metabolism, Caenorhabditis elegans Proteins metabolism
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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