Chain flexibility of medicinal lipids determines their selective partitioning into lipid droplets.

So-Hee Son, Gyuri Park, Junho Lim, Chang Yun Son, Seung Soo Oh, Ju Young Lee

Journal: Nature communications 2022;13(1):3612

PMID: 35750680

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Abstract

In guiding lipid droplets (LDs) to serve as storage vessels that insulate high-value lipophilic compounds in cells, we demonstrate that chain flexibility of lipids determines their selective migration in intracellular LDs. Focusing on commercially important medicinal lipids with biogenetic similarity but structural dissimilarity, we computationally and experimentally validate that LD remodeling should be differentiated between overproduction of structurally flexible squalene and that of rigid zeaxanthin and β-carotene. In molecular dynamics simulations, worm-like flexible squalene is readily deformed to move through intertwined chains of triacylglycerols in the LD core, whereas rod-like rigid zeaxanthin is trapped on the LD surface due to a high free energy barrier in diffusion. By designing yeast cells with either much larger LDs or with a greater number of LDs, we observe that intracellular storage of squalene significantly increases with LD volume expansion, but that of zeaxanthin and β-carotene is enhanced through LD surface broadening; as visually evidenced, the outcomes represent internal penetration of squalene and surface localization of zeaxanthin and β-carotene. Our study shows the computational and experimental validation of selective lipid migration into a phase-separated organelle and reveals LD dynamics and functionalization.

Address: Research Center for Bio-based Chemistry, Korea Research Institute of Chemical Technology (KRICT), 406-30, Jongga-ro, Jung-gu, Ulsan, 44429, Republic of Korea.; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.; Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.; Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.; Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. [email protected].; Division of Advanced Materials Science, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. [email protected].; Institute for Convergence Research and Education in Advanced Technology (I-CREATE), Yonsei University, Incheon, 21983, Republic of Korea. [email protected].; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. [email protected].; Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. [email protected].; Institute for Convergence Research and Education in Advanced Technology (I-CREATE), Yonsei University, Incheon, 21983, Republic of Korea. [email protected].; Research Center for Bio-based Chemistry, Korea Research Institute of Chemical Technology (KRICT), 406-30, Jongga-ro, Jung-gu, Ulsan, 44429, Republic of Korea. [email protected].

DOI: 10.1038/s41467-022-31400-6

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https://www.yeastgenome.org/reference/35750680

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https://antibodies.cancer.gov/detail/CPTC-FOXC2-1

MeSH Terms: Lipid Droplets, Lipid Metabolism, Squalene, Triglycerides, Zeaxanthins, beta Carotene