摘要：SummaryRecently, 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.Graphical AbstractDisplay OmittedHighlights•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 deathCellular Physiology; Cell Biology; Cancer
