ArticleCell reports2022
Loss of heat shock factor initiates intracellular lipid surveillance by actin destabilization.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Heat stress reveals bidirectional cross talk between the heat shock response and UPRER in C. elegans.G3 (Bethesda, Md.) · 2026Article
- Modulation of host proteostasis by Prevotella corporis via induction of the heat shock response.Cell stress & chaperones · 2026Article
- Silencing lipid catabolism determines longevity in response to fasting.Nature communications · 2026Article
- Matrine Inhibits High-Glucose-Diet-Induced Fat Accumulation and Aβ-Mediated Lipid Metabolic Disorder via AAK-2/NHR-49 Pathway inInternational journal of molecular sciences · 2025Article
- Isoform differences drive functional diversity of NHR-49.microPublication biology · 2025Article
- HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling.Nature communications · 2024Article
- Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues.Genes & development · 2024Article
- Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fastediScience · 2024Article
- Early life changes in histone landscape protect against age-associated amyloid toxicities through HSF-1-dependent regulation of lipid metabolism.Nature aging · 2024Article
- A framework for intestinal barrier dysfunction in aging.Nature aging · 2023Article
- Article
- Nuclear hormone receptor NHR-49 is an essential regulator of stress resilience and healthy aging inFrontiers in physiology · 2023Review
- Potential roles for mitochondria-to-HSF1 signaling in health and disease.Frontiers in molecular biosciences · 2023Review
- Exploiting inter-tissue stress signaling mechanisms to preserve organismal proteostasis during aging.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
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