title: 2,2'-dipyridyl induces pexophagy.
abstract: Pexophagy is the selective degradation of peroxisomes for maintaining peroxisome homeostasis within cells. Peroxisome dynamics and pexophagy are important events required to maintain the quality control of peroxisomes, thereby preventing peroxisome-associated diseases. To identify novel pexophagy modulators, we developed a cell-based screening system and selected 2,2'-dipyridyl (2,2-DP) as a candidate molecule. 2,2-DP treatment induced peroxisome degradation as evidenced by an increased number of low-pH autolysosomes originating from peroxisomes and a decrease in the expression of peroxisomal proteins such as catalase, Pex14, and PMP70. The phenotype was defined as pexophagy, because 2,2-DP induced autophagy and inhibition of autophagy significantly reduced the degree of peroxisome degradation. Mechanistically, 2,2-DP-dependent pexophagy seemed to be mediated by iron chelation, since another iron chelator displayed a similar effect on pexophagy, but a copper chelator did not. Notably, iron replenishment prevented 2,2-DP-mediated pexophagy. Taken together, our results suggest that 2,2-DP treatment disrupts peroxisome dynamics and promotes pexophagy through iron depletion.
authors.affiliation: Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: AiLin
authors.initials: A
authors.lastname: Jin
authors.affiliation: Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Joon No
authors.initials: JN
authors.lastname: Lee
authors.affiliation: Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Zoonosis Research Center, Wonkwang University School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: SeongAe
authors.initials: S
authors.lastname: Kwak
authors.affiliation: Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea; Integrated Omics Institute, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Kyung
authors.initials: K
authors.lastname: Song
authors.affiliation: Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea; Integrated Omics Institute, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea. Electronic address: seongkyu642@wku.ac.kr.
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Choe
authors.affiliation: Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea. Electronic address: rkpark@wku.ac.kr.
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
mesh_terms: D015082:2,2'-Dipyridyl / Q000008:administration & dosage*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007502:Iron Chelating Agents; D015082:2,2'-Dipyridyl
keywords: 2,2′-dipyridyl; Autophagy; Iron chelation; Peroxisome dynamics; Pexophagy