Lipid Droplets Maintain Energy Homeostasis and Glioblastoma Growth via Autophagic Release of Stored Fatty Acids.
Lipid Droplets Maintain Energy Homeostasis and Glioblastoma Growth via Autophagic Release of Stored Fatty Acids.
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脂滴通过自噬释放储存的脂肪酸来维持能量平衡和胶质母细胞瘤的生长。
DOI：
10.1016/j.isci.2020.101569
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发表时间：
2020-10-23
期刊：
影响因子：
5.8
通讯作者：
Guo D
中科院分区：
文献类型：
--
作者：
Wu X;Geng F;Cheng X;Guo Q;Zhong Y;Cloughesy TF;Yong WH;Chakravarti A;Guo D
最近，通过观察人类肿瘤中的大量脂滴(LDs)，包括最致命的原发脑肿瘤-胶质母细胞瘤(GBM)，进一步证明了脂代谢重编程在恶性肿瘤中的存在。然而，LDS在肿瘤细胞中所起的作用仍不清楚。在这里，我们展示了甘油三酯(TG)，LDS的主要成分，作为支持GBM细胞生存的关键能量储存库。当葡萄糖降低时，GBM细胞的TG/LDS迅速降低，而抑制脂肪酸氧化或自噬导致TG/LDS的积聚，并强烈促进GBM细胞的死亡。免疫荧光成像和延时视频显示，LDS被自噬降解，释放游离脂肪酸，然后转移到线粒体中产生能量。我们的研究表明，自噬介导的TG/LDS的水解在葡萄糖减少时维持能量平衡和GBM存活，这表明在治疗GBM时限制TG/LDS的利用可能是必要的。TG/LDS作为GBM肿瘤的能量储存库TG/LDS被自噬降解以维持GBM的存活当葡萄糖水平降低时，TG/LDS水解释放进入线粒体产生能量的脂肪酸抑制自噬导致TG/LD积聚和GBM细胞死亡细胞生理学；细胞生物学；癌症
Recently, lipid metabolism reprogramming has been further evidenced in malignancies via the observation of large amounts of lipid droplets (LDs) in human tumors, including in glioblastoma (GBM), the most lethal primary brain tumor. However, the role played by LDs in tumor cells remains unknown. Here, we show that triglycerides (TG), the major components of LDs, serve as a critical energy reservoir to support GBM cell survival. TG/LDs rapidly diminished in GBM cells upon glucose reduction, whereas inhibiting fatty acid oxidation or autophagy resulted in the accumulation of TG/LDs and strongly potentiated GBM cell death. Immunofluorescence imaging and time-lapse videos showed that LDs are hydrolyzed by autophagy to release free fatty acids that mobilize into mitochondria for energy production. Our study demonstrates that autophagy-mediated hydrolysis of TG/LDs maintains energy homeostasis and GBM survival upon glucose reduction, suggesting that limiting TG/LDs utilization might be necessary upon treating GBM. TG/LDs function as energy reservoir for GBM tumors TG/LDs are hydrolyzed by autophagy to maintain GBM survival when glucose levels decrease TG/LD hydrolysis releases fatty acids that enter into mitochondria for energy production Inhibiting autophagy causes TG/LD accumulation and GBM cell death Cellular Physiology; Cell Biology; Cancer
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影响因子：
64.8
作者：
Lee, Jae Man;Wagner, Martin;Xiao, Rui;Kim, Kang Ho;Feng, Dan;Lazar, Mitchell A.;Moore, David D.
通讯作者：
Moore, David D.
DOI：
10.1186/s40880-018-0301-4
发表时间：
2018-05-21
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Cheng C;Geng F;Cheng X;Guo D
通讯作者：
Guo D
影响因子：
29
作者：
Cheng, Xiang;Geng, Feng;Guo, Deliang
通讯作者：
Guo, Deliang
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
5
作者：
Brace LE;Vose SC;Stanya K;Gathungu RM;Marur VR;Longchamp A;Treviño-Villarreal H;Mejia P;Vargas D;Inouye K;Bronson RT;Lee CH;Neilan E;Kristal BS;Mitchell JR
通讯作者：
Mitchell JR