LAPTM5-dependent lipophagy enhances ferroptosis sensitivity in glioma cells

Background Lysosomal-associated protein transmembrane 5 (LAPTM5) is a transmembrane protein predominantly localized to late endosomes and lysosomes, with preferential expression in hematopoietic cells. Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death (PCD) that is driven by the lethal accumulation of lipid peroxides. Many studies have shown that ferroptosis is dependent on autophagy. Lipophagy is a selective form of autophagy by degrading lipid droplets (LDs) within autophagic vesicles to regulate lipid balance. Lipophagy can promote RAS-selective lethal 3 (RSL3)-induced ferroptosis. However, whether LAPTM5 regulates lipophagy to sensitize glioma cells to ferroptosis remains to be explored. Therefore, the objective of our study was to evaluate the potential role of LAPTM5 in ferroptosis. Methods The expression profile of LAPTM5 in human glioma tissues was analyzed by using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and immunohistochemistry. Glioma cells were treated with ferroptosis inducer erastin, and then the cell viability, glutathione (GSH), and malondialdehyde (MDA) were detected. Lipophagy was tested by laser confocal microscopy and proteins expression were detected by western blot. Results Elevated expression of LAPTM5 was observed in glioma tissues compared to normal brain tissues, and its high expression level was associated with poorer patient prognosis. LAPTM5 promoted lipophagy in glioma cells. LAPTM5 enhanced the sensitivity of glioma cells to ferroptosis inducer erastin, while suppression of lipophagy inhibited LAPTM5-mediated sensitization to erastin. Conclusions The finding that glioma cells with high LAPTM5 expression were more sensitive to ferroptosis inducers suggests that glioma patients with high LAPTM5 expression may be more responsive to ferroptosis-inducing therapies.