title: Mitochondrial fragmentation caused by phenanthroline promotes mitophagy.
abstract: Mitochondrial dynamics and mitophagy are thought to be important events for the quality control of mitochondria and mitochondria-associated diseases. To identify novel mitophagy modulators, we developed a cell-based screening system and selected 1,10-phenanthroline (Phen) as a target molecule. Phen treatment highly induced mitochondrial fragmentation and mitochondrial dysfunctions in a Drp1 dependent manner. Phen treatment also increased autophagy. Moreover, prolonged exposure of Phen increased mitochondria clearance through mitophagy. Phen-mediated loss of mitochondrial mass was more reduced in ATG5 deficient cells than in wild type cells. In addition, down-regulation of Drp1 decreased autophagy activation, suggesting that mitochondrial fission is involved in Phen-mediated mitophagy. Thus, our results demonstrate that the disruption of mitochondrial dynamics and mitochondrial dysfunctions provokes mitophagy in Phen-treated cells.
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-Do, South Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Shin
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Kim
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jo
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D000818:Animals; D000071187:Autophagy-Related Protein 5; D002460:Cell Line; D002614:Chelating Agents / Q000009:adverse effects*; D015536:Down-Regulation / Q000187:drug effects; D034281:Dynamins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D063154:Mitochondrial Dynamics / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects*; D010618:Phenanthrolines / Q000494:pharmacology*
chemical_list: C502778:ATG5 protein, human; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D002614:Chelating Agents; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D010618:Phenanthrolines; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; C486391:Dnm1l protein, mouse; D034281:Dynamins; C025205:1,10-phenanthroline