Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association
Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association
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DOI：
10.1073/pnas.1903642116
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发表时间：
2019-08-20
影响因子：
11.1
通讯作者：
Baumeister, Wolfgang
中科院分区：
文献类型：
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作者：
Mahamid, Julia;Tegunov, Dimitry;Baumeister, Wolfgang
脂滴（Lipid droplets，LD）是一种普遍存在的细胞器，是细胞脂质代谢和运输的中枢。这种作用与它们与几种细胞器的相互作用密切相关。在这里，我们提供了一个系统的和定量的结构描述的LD在其原生状态的HeLa细胞，使细胞冷冻电子显微镜。LD由三酰甘油（TAG）和胆固醇酯（CE）的疏水中性脂质混合物组成，周围环绕着单层磷脂。我们表明，在正常的培养条件下，LD是无定形的，并且它们在生理温度下在某些细胞周期阶段或代谢情况下转变成围绕无定形核心的近晶液晶相。在确定了3.5 nm的晶格间距和低于43 ℃的相变温度之后，我们将液晶相归因于CE。我们认为，有丝分裂停滞和饥饿下，相对CE水平增加，大概是由于TAG代谢产物的膜合成和线粒体呼吸，分别支持直接可视化的LD-线粒体膜接触位点的消费。我们推测，结构相变可能有一个主要的影响，在LD中的脂质酶或脂质转运蛋白的可及性。这些可能会限制在近晶相，影响脂质与周围膜的交换速率，并导致LD相关蛋白质的不同表面占有率。因此，LD的组成和由此产生的内部结构预计将在其作为细胞脂质通量枢纽的功能中发挥关键作用。
Lipid droplets (LDs) are ubiquitous organelles comprising a central hub for cellular lipid metabolism and trafficking. This role is tightly associated with their interactions with several cellular organelles. Here, we provide a systematic and quantitative structural description of LDs in their native state in HeLa cells enabled by cellular cryoelectron microscopy. LDs consist of a hydrophobic neutral lipid mixture of triacylglycerols (TAG) and cholesteryl esters (CE), surrounded by a single monolayer of phospholipids. We show that under normal culture conditions, LDs are amorphous and that they transition into a smectic liquid-crystalline phase surrounding an amorphous core at physiological temperature under certain cell-cycle stages or metabolic scenarios. Following determination of the crystal lattice spacing of 3.5 nm and of a phase transition temperature below 43 degrees C, we attributed the liquid-crystalline phase to CE. We suggest that under mitotic arrest and starvation, relative CE levels increase, presumably due to the consumption of TAG metabolites for membrane synthesis and mitochondrial respiration, respectively, supported by direct visualization of LD-mitochondrial membrane contact sites. We hypothesize that the structural phase transition may have a major impact on the accessibility of lipids in LDs to enzymes or lipid transporters. These may become restricted in the smectic phase, affecting the exchange rate of lipids with surrounding membranes and lead to a different surface occupancy of LD-associated proteins. Therefore, the composition and the resulting internal structure of LDs is expected to play a key role in their function as hubs of cellular lipid flux.