The architecture of Cidec-mediated interfaces between lipid droplets
Iva Ganeva,
Koini Lim,
Jerome Boulanger,
Patrick C. Hoffmann,
Olivia Muriel,
Alicia C. Borgeaud,
Wim J.H. Hagen,
David B. Savage,
Wanda Kukulski
Affiliations
Iva Ganeva
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland
Koini Lim
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK
Jerome Boulanger
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
Patrick C. Hoffmann
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
Olivia Muriel
Electron Microscopy Facility, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland; Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland
Alicia C. Borgeaud
Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland
Wim J.H. Hagen
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
David B. Savage
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK; Corresponding author
Wanda Kukulski
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland; Corresponding author
Summary: Lipid droplets (LDs) are intracellular organelles responsible for storing surplus energy as neutral lipids. Their size and number vary enormously. In white adipocytes, LDs can reach 100 μm in diameter, occupying >90% of the cell. Cidec, which is strictly required for the formation of large LDs, is concentrated at interfaces between adjacent LDs and facilitates directional flux of neutral lipids from the smaller to the larger LD. The mechanism of lipid transfer is unclear, in part because the architecture of interfaces between LDs remains elusive. Here we visualize interfaces between LDs by electron cryo-tomography and analyze the kinetics of lipid transfer by quantitative live fluorescence microscopy. We show that transfer occurs through closely apposed monolayers, is slowed down by increasing the distance between the monolayers, and follows exponential kinetics. Our data corroborate the notion that Cidec facilitates pressure-driven transfer of neutral lipids through two “leaky” monolayers between LDs.
