Triamterene induces autophagic degradation of lysosome by exacerbating lysosomal integrity

The maintenance of lysosomal integrity is essential for lysosome function and cell fate. Damaged lysosomes are degraded by lysosomal autophagy, lysophagy. The mechanism underlying lysophagy remains largely unknown; this study aimed to contribute to the understanding of this topic. A cell-based scree...

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Bibliographic Details
Published in:Archives of pharmacal research 2021, 44(6), , pp.621-631
Main Authors: Park, Na Yeon, Jo, Doo Sin, Kim, Yong Hwan, Bae, Ji-Eun, Kim, Joon Bum, Park, Hyun Jun, Choi, Ji Yeon, Lee, Ha Jung, Chang, Jeong Ho, Bunch, Heeyoun, Jeon, Hong Bae, Jung, Yong-Keun, Cho, Dong-Hyung
Format: Article
Language:English
Subjects:
Medicine
Pharmacology/Toxicology
Pharmacy
Research Article
약학
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Summary:The maintenance of lysosomal integrity is essential for lysosome function and cell fate. Damaged lysosomes are degraded by lysosomal autophagy, lysophagy. The mechanism underlying lysophagy remains largely unknown; this study aimed to contribute to the understanding of this topic. A cell-based screening system was used to identify novel lysophagy modulators. Triamterene (6-phenylpteridine-2,4,7-triamine) was identified as one of the most potent lysophagy inducers from the screening process. We found that triamterene causes lysosomal rupture without affecting other cellular organelles and increases autophagy flux in HepG2 cells. Damaged lysosomes in triamterene-treated cells were removed by autophagy-mediated pathway, which was inhibited by depletion of the autophagy regulator, ATG5 or SQSTM1. In addition, treatment of triamterene decreased the integrity of lysosome and cell viability, which were rescued by removing the triamterene treatment in HepG2 cells. Hence, our data suggest that triamterene is a novel lysophagy inducer through the disruption of lysosomal integrity.
ISSN:0253-6269
1976-3786
DOI:10.1007/s12272-021-01335-5