ArticleProceedings of the National Academy of Sciences of the United States of America2020
Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- FAHFAs are detected in postprandial chylomicron and VLDL fractions and can be released from TG estolides by LPL in vitro.Journal of lipid research · 2026Article
- Acyl-CoA thioesterases and their derived lipid mediators: linking Acyl-CoA metabolic reprogramming to the tumor microenvironment.Frontiers in immunology · 2026Review
- Porcine GWAS identifies ACOT11 as regulator for macrophage IL-1β maturation via IFNGR2 palmitoylation.Science China. Life sciences · 2025Article
- CottonGenes · 2025Article
- Arabidopsis PROTODERMAL FACTOR2 binds lysophosphatidylcholines and transcriptionally regulates phospholipid metabolism.The New phytologist · 2024Article
- Identification of transcription factor BnHDG4-A08 as a novel candidate associated with the accumulation of oleic, linoleic, linolenic, and erucic acid in Brassica napus.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2024Article
- Structure, function, and lipid sensing activity in the thioesterase superfamily.Biochemical Society transactions · 2024Review
- High-throughput screening identifies small molecule inhibitors of thioesterase superfamily member 1: Implications for the management of non-alcoholic fatty liver disease.Molecular metabolism · 2023Article
- HD-Zip IV transcription factors: Drivers of epidermal cell fate integrate metabolic signals.Current opinion in plant biology · 2023Review
- Acceptors and Effectors Alter Substrate Inhibition Kinetics of a Plant Glucosyltransferase NbUGT72AY1 and Its Mutants.International journal of molecular sciences · 2023Article
- The START domain potentiates HD-ZIPIII transcriptional activity.The Plant cell · 2023Article
- Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.Nature communications · 2023Article
- The START domain mediates Arabidopsis GLABRA2 dimerization and turnover independently of homeodomain DNA binding.Plant physiology · 2022Article
- Human CYP2B6 produces oxylipins from polyunsaturated fatty acids and reduces diet-induced obesity.PloS one · 2022Article
- Identifying Cancer-Relevant Mutations in the DLC START Domain Using Evolutionary and Structure-Function Analyses.International journal of molecular sciences · 2020Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Nonshivering thermogenesis occurs in brown adipose tissue to generate heat in response to cold ambient temperatures. Thioesterase superfamily member 1 (Them1) is transcriptionally up-regulated in brown adipose tissue upon exposure to the cold and suppresses thermogenesis in order to conserve energy reserves. It hydrolyzes long-chain fatty acyl-CoAs that are derived from lipid droplets, preventing their use as fuel for thermogenesis. In addition to its enzymatic domains, Them1 contains a C-terminal StAR-related lipid transfer (START) domain with unknown ligand or function. By complementary biophysical approaches, we show that the START domain binds to long-chain fatty acids, products of Them1's enzymatic reaction, as well as lysophosphatidylcholine (LPC), lipids shown to activate thermogenesis in brown adipocytes. Certain fatty acids stabilize the START domain and allosterically enhance Them1 catalysis of acyl-CoA, whereas 18:1 LPC destabilizes and inhibits activity, which we verify in cell culture. Additionally, we demonstrate that the START domain functions to localize Them1 near lipid droplets. These findings define the role of the START domain as a lipid sensor that allosterically regulates Them1 activity and spatially localizes it in proximity to the lipid droplet.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.