脂滴形成的动力学模型表明膜磷脂具有关键功能。

Hermann-Georg Holzhütter
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引用次数: 0

摘要

细胞将三酰甘油(TAG)储存在脂滴(LD)中。描述内质网(ER)膜上完整 LD 形成的动态模型尚不存在。本文提出了一个 LD 合成的生物化学-生物物理模型。该模型将 TAG 在 ER 膜上随时间变化的积累描述为潜在 LD(pLD)的形成,该潜在 LD 由膜的内外单层球形盖所包围。潜在低密度区的扩张速度取决于 TAG 的供应、ER 膜的弹性特性以及磷脂(PL)向覆盖膜帽的单层的招募。模型模拟提供了以下启示:(a)盖单层表面张力的微小差异足以完全驱动 pLD 向细胞膜或管腔扩张。(b) 有选择性地减少向腔内单层提供的 PL 可确保稳定地形成细胞质 LD,而与 ER 膜的弹性-机械特性变化无关。(c) 向细胞膜单层供应 TAG 的速率对 LD 的大小和成熟时间有重大影响,但对每个 LD 的 TAG 输出没有显著影响。向 pLDs 的帽单层招募额外的 PLs 对 LDs 的出芽方向、大小和成熟时间具有关键性的控制作用。细胞获得额外 LD 起始点的能力似乎是应对高浓度潜在毒性游离脂肪酸的关键。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dynamical modelling of lipid droplet formation suggests a key function of membrane phospholipids.

Cells store triacylglycerol (TAG) within lipid droplets (LDs). A dynamic model describing complete LD formation at the endoplasmic reticulum (ER) membrane does not yet exist. A biochemical-biophysical model of LD synthesis is proposed. It describes the time-dependent accumulation of TAG in the ER membrane as the formation of a potential LD (pLD) bounded by spherical caps of the inner and outer monolayers of the membrane. The expansion rate of the pLD depends on the TAG supply, the elastic properties of the ER membrane, and the recruitment of phospholipids (PLs) to the cap-covering monolayers. Model simulations provided the following insights: (a) Marginal differences in the surface tension of the cap monolayers are sufficient to fully drive the expansion of the pLD towards the cytosol or lumen. (b) Selective reduction of PL supply to the luminal monolayer ensures stable formation of cytosolic LDs, irrespective of variations in the elasto-mechanical properties of the ER membrane. (c) The rate of TAG supply to the cytosolic monolayer has a major effect on the size and maturation time of LDs but has no significant effect on the TAG export per individual LD. The recruitment of additional PLs to the cap monolayers of pLDs critically controls the budding direction, size, and maturation time of LDs. The ability of cells to acquire additional LD initiation sites appears to be key to coping with acutely high levels of potentially toxic free fatty acids.

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