Author:
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
Abstract
AbstractThe 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.
Funder
National Research Foundation of Korea
Ministry of Education
Publisher
Springer Science and Business Media LLC
Subject
Organic Chemistry,Drug Discovery,Molecular Medicine
Cited by
3 articles.
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