The role of caveolin-1 in lipid droplets and their biogenesis
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The role of caveolin-1 in lipid droplets and their biogenesis. / Pezeshkian, Weria; Chevrot, Guillaume; Khandelia, Himanshu.
I: Chemistry and Physics of Lipids, Bind 211, 03.2018, s. 93-99.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The role of caveolin-1 in lipid droplets and their biogenesis
AU - Pezeshkian, Weria
AU - Chevrot, Guillaume
AU - Khandelia, Himanshu
PY - 2018/3
Y1 - 2018/3
N2 - We address unresolved questions of the energetics and mechanism of lipid droplet (LD) biogenesis, and of the role of caveolins in the endoplasmic reticulum (ER) and in mature LDs. LDs are eukaryotic repositories of neutral lipids, which are believed to be synthesised in the ER. We investigate the effects of a curvature-inducing protein, caveolin-1, on the formation and structure of a spontaneously aggregated triolein (TO) lipid lens in a flat lipid bilayer using molecular dynamics (MD) simulations. A truncated form of caveolin-1 (Cav1) localises on the interface between the spontaneously formed TO aggregate and the bulk bilayer, and thins the bilayer at the edge of the aggregate, which may contribute to lowering the energy barrier for pinching off the aggregate from the host bilayer. Simulations of fully mature LDs do not conclusively establish the optimal localisation of Cav1 in LDs, but when Cav1 is in the LD core, the distribution of both neutral lipids in the LD core, and of phospholipids on the engulfing monolayer are altered significantly. Our simulations provide an unprecedented molecular description of the distribution and dynamics of various lipid species in both mature LDs and in the nascent LD inside the bilayer.
AB - We address unresolved questions of the energetics and mechanism of lipid droplet (LD) biogenesis, and of the role of caveolins in the endoplasmic reticulum (ER) and in mature LDs. LDs are eukaryotic repositories of neutral lipids, which are believed to be synthesised in the ER. We investigate the effects of a curvature-inducing protein, caveolin-1, on the formation and structure of a spontaneously aggregated triolein (TO) lipid lens in a flat lipid bilayer using molecular dynamics (MD) simulations. A truncated form of caveolin-1 (Cav1) localises on the interface between the spontaneously formed TO aggregate and the bulk bilayer, and thins the bilayer at the edge of the aggregate, which may contribute to lowering the energy barrier for pinching off the aggregate from the host bilayer. Simulations of fully mature LDs do not conclusively establish the optimal localisation of Cav1 in LDs, but when Cav1 is in the LD core, the distribution of both neutral lipids in the LD core, and of phospholipids on the engulfing monolayer are altered significantly. Our simulations provide an unprecedented molecular description of the distribution and dynamics of various lipid species in both mature LDs and in the nascent LD inside the bilayer.
KW - Molecular dynamics simulations
KW - Lipid droplets
KW - Lipid droplet biogenesis
KW - Lipid sorting
KW - Caveolin
KW - Curvature
KW - Coarse-grained simulations
KW - COARSE-GRAINED MODEL
KW - FORCE-FIELD
KW - CHOLESTEROL
KW - SIMULATIONS
KW - ADIPOCYTES
KW - DYNAMICS
KW - REVEALS
KW - BILAYER
KW - PROTEIN
U2 - 10.1016/j.chemphyslip.2017.11.010
DO - 10.1016/j.chemphyslip.2017.11.010
M3 - Journal article
VL - 211
SP - 93
EP - 99
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
SN - 0009-3084
ER -
ID: 316865892