Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity.
Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity.
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DOI：
10.1016/j.cub.2013.06.032
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发表时间：
2013-08-05
期刊：
影响因子：
9.2
通讯作者：
Pol, Albert
中科院分区：
文献类型：
--
作者：
Herms, Albert;Bosch, Marta;Ariotti, Nicholas;Reddy, Babu J. N.;Fajardo, Alba;Fernandez-Vidal, Andrea;Alvarez-Guaita, Anna;Fernandez-Rojo, Manuel Alejandro;Rentero, Carles;Tebar, Francesc;Enrich, Carlos;Geli, Maria-Isabel;Parton, Robert G.;Gross, Steven P.;Pol, Albert
脂滴（Lipid drops，LD）是一种收集、储存和供应脂质的动态细胞器。LD在细胞与环境之间发生的脂质交换中具有核心作用，并为细胞提供用于能量代谢、膜合成和产生脂质衍生分子（如脂蛋白或激素）的底物。然而，脂质衍生的代谢物也引起进行性脂毒性;活性氧（ROS）的积累、内质网应激、线粒体功能障碍和细胞死亡。LD的细胞内积累是包括肥胖症、脂肪变性、糖尿病、肌病和动脉硬化在内的普遍人类疾病的标志。事实上，非酒精性脂肪肝是成年人肝功能异常的最常见原因。脂毒性逐渐促进细胞气球样变和紊乱、巨线粒体和肝细胞中马洛里透明蛋白的积累以及肝脏中的炎症、纤维化和肝硬化。在这里，使用共聚焦显微镜，连续块面扫描电子显微镜，流式细胞术，我们表明，LD积累是异质性的细胞群内，并遵循正偏态分布。控制脂解、脂肪酸氧化和蛋白质合成的生物化学网络中的脂质可用性和波动有助于细胞与细胞的异质性。重要的是，这种可逆的变异性产生了一个有效收集和储存脂质的细胞亚群。这种高脂亚群积累了更多的LD，更多的ROS，并降低了对群体的脂毒性风险，而不损害整体脂质稳态，因为高脂细胞可以向其他细胞提供储存的脂质。总之，我们证明了细胞群中的脂肪储存区室化，并提出这是一种保护性的社会组织，以减少脂毒性。
Lipid droplets (LDs) are dynamic organelles that collect, store, and supply lipids. LDs have a central role in the exchange of lipids occurring between the cell and the environment, and provide cells with substrates for energy metabolism, membrane synthesis, and production of lipid-derived molecules such as lipoproteins or hormones. However, lipid-derived metabolites also cause progressive lipotoxicity; accumulation of reactive oxygen species (ROS), endoplasmic reticulum stress, mitochondrial malfunctioning, and cell death. Intracellular accumulation of LDs is a hallmark of prevalent human diseases including obesity, steatosis, diabetes, myopathies, and arteriosclerosis. Indeed, non-alcoholic fatty liver disease is the most common cause of abnormal hepatic function among adults. Lipotoxicity gradually promotes cellular ballooning and disarray, megamitochondria, and accumulation of Mallory’s hyaline in hepatocytes and inflammation, fibrosis, and cirrhosis in the liver. Here, using confocal microscopy, serial-block-face scanning electron microscopy, and flow-cytometry we show that LD accumulation is heterogeneous within a cell population and follows a positive skewed distribution. Lipid availability and fluctuations in biochemical networks controlling lipolysis, fatty acid oxidation, and protein synthesis, contribute to cell-to-cell heterogeneity. Critically, this reversible variability generates a subpopulation of cells that effectively collect and store lipids. This high-lipid subpopulation accumulates more LDs, more ROS, and reduces the risk of lipotoxicity to the population without impairing overall lipid homeostasis, since high-lipid cells can supply stored lipids to the other cells. In conclusion, we demonstrate fat storage compartmentalization within a cell population and propose that this is a protective social organization to reduce lipotoxicity.
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作者：
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发表时间：
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影响因子：
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DOI：
10.1083/jcb.200904140
发表时间：
2009-11-02
期刊：
The Journal of cell biology
影响因子：
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