2. Academic Validation
  3. Triamterene induces autophagic degradation of lysosome by exacerbating lysosomal integrity

Triamterene induces autophagic degradation of lysosome by exacerbating lysosomal integrity

  • Arch Pharm Res. 2021 Jun;44(6):621-631. doi: 10.1007/s12272-021-01335-5.
Na Yeon Park 1,  Doo Sin Jo 1,  Yong Hwan Kim 1,  Ji-Eun Bae 2,  Joon Bum Kim 1,  Hyun Jun Park 1,  Ji Yeon Choi 1,  Ha Jung Lee 1,  Jeong Ho Chang 3,  Heeyoun Bunch 4,  Hong Bae Jeon 5,  Yong-Keun Jung 6,  Dong-Hyung Cho 7 8
Affiliations

Affiliations

  • 1 School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, 80 Daehakro Bukgu, Daegu, 41566, Republic of Korea.
  • 2 Brain Science and Engineering Institute, Kyungpook National University, Daegu, 41566, Republic of Korea.
  • 3 Department of Biology Education, Kyungpook National University, Daegu, 41566, Republic of Korea.
  • 4 School of Applied Biosciences, College of Agriculture and Life Science, Kyungpook National University, Daegu, 41566, Republic of Korea.
  • 5 Stem Cell Institute, ENCell Co. Ltd, Seoul, 06072, Republic of Korea.
  • 6 School of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • 7 School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, 80 Daehakro Bukgu, Daegu, 41566, Republic of Korea. [email protected].
  • 8 Brain Science and Engineering Institute, Kyungpook National University, Daegu, 41566, Republic of Korea. [email protected].
PMID: 34100261 DOI: 10.1007/s12272-021-01335-5
Abstract

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.

Keywords

Autophagy; HepG2 cells; LLOMe; Lysophagy; Lysosomal integrity; Triamterene.

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