Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids
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Horvitz_Acyl-coa.pdf
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Author(s)
Li, Zhijie
Sun, Fang
Chen, Sidi
Rothe, Michael
Menzel, Ralph
Ma, Dengke
Lu, Alice Y.
Horvitz, Howard Robert
Sun, Fei, S.B. Massachusetts Institute of Technology
Date Issued
May 2015
Journal
Cell
Publisher
Elsevier
Citation
Ma, Dengke K. et al. “Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.” Cell 161.5 (2015): 1152–1163.
Version
Author's final manuscript
Abstract
Cells adapt to temperature shifts by adjusting levels of lipid desaturation and membrane fluidity. This fundamental process occurs in nearly all forms of life, but its mechanism in eukaryotes is unknown. We discovered that the evolutionarily conserved C. elegans gene acdh-11 (acyl CoAdehydrogenase, ACDH) facilitates heat adaptation by regulating the lipid desaturase FAT-7. Human ACDH deficiency causes the most common inherited disorders of fatty acid oxidation, with syndromes that are exacerbated by hyperthermia. Heat up-regulates acdh-11 expression to
decrease fat-7 expression. We solved the high-resolution crystal structure of ACDH-11 and established the molecular basis of its selective and high-affinity binding to C11/C12-chain fatty acids. ACDH-11 sequesters C11/C12-chain fatty acids and prevents these fatty acids from activating nuclear hormone receptors and driving fat-7 expression. Thus, the ACDH-11 pathway drives heat adaptation by linking temperature shifts to regulation of lipid desaturase levels and membrane fluidity via an unprecedented mode of fatty acid signaling.
MIT Department
Massachusetts Institute of Technology. Department of Biology
McGovern Institute for Brain Research at MIT
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2015.04.026
