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Lipid landscapes and pipelines in membrane homeostasis

Abstract

The lipid composition of cellular organelles is tailored to suit their specialized tasks. A fundamental transition in the lipid landscape divides the secretory pathway in early and late membrane territories, allowing an adaptation from biogenic to barrier functions. Defending the contrasting features of these territories against erosion by vesicular traffic poses a major logistical problem. To this end, cells evolved a network of lipid composition sensors and pipelines along which lipids are moved by non-vesicular mechanisms. We review recent insights into the molecular basis of this regulatory network and consider examples in which malfunction of its components leads to system failure and disease.

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Figure 1: Membranes of early and late secretory organelles have contrasting lipid compositions and physical properties.
Figure 2: Membrane lipid biosynthesis.
Figure 3: Lipid composition sensors in biogenic organelles.
Figure 4: Lipid pipelines operated by lipid transfer proteins.
Figure 5: Crosstalk between plasma membrane sphingolipid levels and transbilayer lipid asymmetry.

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Acknowledgements

Work in the authors laboratories is supported by the European Union (MC-ITN Sphingonet Project 289278 to J.C.H.), the Deutsche Forschungsgemeinschaft (SFB944-P14 to J.C.H.) and the National Institutes of Health (grant GM071041 to A.K.M.).

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Holthuis, J., Menon, A. Lipid landscapes and pipelines in membrane homeostasis. Nature 510, 48–57 (2014). https://doi.org/10.1038/nature13474

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