4.6 Article

Thyroid hormone upregulates LAMP2 expression and lysosome activity

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2023.04.061

Keywords

Thyroid hormone; Lysosome; LAMP2; Vesicle trafficking; ER stress

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Recent studies have shown that T3 can promote rapid turnover of lysosomes and expression of numerous lysosomal genes, enhancing lysosomal activity in digesting any additional autophagosomal burden. Lysosomes play an important role in autophagy, but limited research has been conducted on this topic.
Thyroid hormone (T3)-induced autophagy and its biological significance have been extensively investi-gated in recent years. However, limited studies to date have focused on the important role of lysosomes in autophagy. In this study, we explored the effects of T3 on lysosomal protein expression and trafficking in detail. Our findings showed that T3 activates rapid lysosomal turnover and expression of numerous lysosomal genes, including TFEB , LAMP2 , ARSB , GBA , PSAP , ATP6V0B , ATP6V0D1 , ATP6V1E1 , CTSB , CTSH , CTSL , and CTSS , in a thyroid hormone receptor-dependent manner. In a murine model, LAMP2 protein was specifically induced in mice with hyperthyroidism. T3-promoted microtubule assembly was signif-icantly disrupted by vinblastine, resulting in accumulation of the lipid droplet marker PLIN2. In the presence of the lysosomal autophagy inhibitors bafilomycin A1, chloroquine and ammonium chloride, we observed substantial accumulation of LAMP2 but not LAMP1 protein. T3 further enhanced the protein levels of ectopically expressed LAMP1 and LAMP2. Upon knockdown of LAMP2, cavities of lysosomes and lipid droplets accumulated in the presence of T3 , although the changes in LAMP1 and PLIN2 expression were less pronounced. More specifically, the protective effect of T3 against ER stress-induced death was abolished by knockdown of LAMP2. Our collective results indicate that T3 not only promotes lysosomal gene expression but also LAMP protein stability and microtubule assembly, leading to enhancement of lysosomal activity in digesting any additional autophagosomal burden.(c) 2023 Elsevier Inc. All rights reserved.

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