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Updated: Nov 2, 2025

Using Caenorhabditis elegans as a Model System to Study Protein Homeostasis in a Multicellular Organism
Published on: December 18, 2013
Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in
Yue Li1,2, Norihiro Imai3, Hayley T Nicholls3
1Division of General Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Abstract:
In brown adipose tissue, thermogenesis is suppressed by thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase. Them1 is highly upregulated by cold ambient temperature, where it reduces fatty acid availability and limits thermogenesis. Here, we show that Them1 regulates metabolism by undergoing conformational changes in response to β-adrenergic stimulation that alter Them1 intracellular distribution. Them1 forms metabolically active puncta near lipid droplets and mitochondria. Upon stimulation, Them1 is phosphorylated at the N-terminus, inhibiting puncta formation and activity and resulting in a diffuse intracellular localization. We show by correlative light and electron microscopy that Them1 puncta are biomolecular condensates that are inhibited by phosphorylation. Thus, Them1 forms intracellular biomolecular condensates that limit fatty acid oxidation and suppress thermogenesis. During a period of energy demand, the condensates are disrupted by phosphorylation to allow for maximal thermogenesis. The stimulus-coupled reorganization of Them1 provides fine-tuning of thermogenesis and energy expenditure.
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