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.
Keywords:
Peroxisome; Phenanthroline; ROS; autophagy; pexophagy.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Autophagy / drug effects*
-
Autophagy / genetics
-
Autophagy-Related Protein 5
-
Catalase / genetics
-
Catalase / metabolism
-
Cell Line, Tumor
-
Chelating Agents / pharmacology*
-
Endoplasmic Reticulum / drug effects
-
Endoplasmic Reticulum / metabolism
-
Fibroblasts / drug effects
-
Fibroblasts / metabolism
-
Gene Expression Regulation
-
Golgi Apparatus / drug effects
-
Golgi Apparatus / metabolism
-
Hepatocytes / drug effects
-
Hepatocytes / metabolism
-
High-Throughput Screening Assays
-
Humans
-
Mice
-
Microtubule-Associated Proteins / genetics
-
Microtubule-Associated Proteins / metabolism
-
Peroxisomes / drug effects*
-
Peroxisomes / metabolism
-
Phenanthrolines / pharmacology*
-
Reactive Oxygen Species / agonists*
-
Reactive Oxygen Species / metabolism
-
Signal Transduction
Substances
-
ATG5 protein, human
-
Autophagy-Related Protein 5
-
Chelating Agents
-
MAP1LC3A protein, human
-
Microtubule-Associated Proteins
-
Phenanthrolines
-
Reactive Oxygen Species
-
Catalase
-
1,10-phenanthroline