title: Pexophagy is induced by increasing peroxisomal reactive oxygen species in 1'10-phenanthroline-treated cells.
abstract: Although autophagy regulates the quality and quantity of cellular organelles, the regulatory mechanisms of peroxisomal autophagy remain largely unknown. In this study, we developed a cell-based image screening assay, and identified 1,10-phenanthroline (Phen) as a novel pexophagy inducer from chemical library screening. Treatment with Phen induces selective loss of peroxisomes but not endoplasmic reticulum and Golgi apparatus in hepatocytes. In addition, Phen increases autophagic engulfment of peroxisomes in an ATG5 dependent manner. Interestingly, treatment of Phen excessively produces peroxisomal reactive oxygen species (ROS), and inhibition of the ROS suppresses loss of peroxisome in Phen-treated cells. Taken together, these results suggest that Phen triggers pexophagy by enhancing peroxisomal ROS.
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi, South Korea.
authors.forename: Doo Sin
authors.initials: DS
authors.lastname: Jo
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Bae
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi, South Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi, South Korea.
authors.forename: Hae Mi
authors.initials: HM
authors.lastname: Seo
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi, South Korea.
authors.forename: Han Byeol
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Research Institute for Future Medicine Stem Cell & Regenerative Medicine Center, Samsung Medical Center, Seoul, South Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi, South Korea. Electronic address: shinarago@khu.ac.kr.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi, South Korea. Electronic address: dhcho@khu.ac.kr.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071187:Autophagy-Related Protein 5; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism; D010618:Phenanthrolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D002614:Chelating Agents; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D002374:Catalase; C025205:1,10-phenanthroline
keywords: Peroxisome; Phenanthroline; ROS; autophagy; pexophagy