Lipid Droplets Maintain Energy Homeostasis and Glioblastoma Growth Via Autophagic Release of Stored Fatty Acids

Overview

Journal iScience

Publisher Cell Press

Date 2020 Oct 21

PMID 33083736

Citations 57

Authors

Xiaoning Wu

Feng Geng

Xiang Cheng

Qiang Guo

Yaogang Zhong

Timothy F Cloughesy

William H Yong

Arnab Chakravarti

Deliang Guo

Affiliations

Soon will be listed here.

Abstract

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.

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