Mitochondrial fragmentation caused by phenanthroline promotes mitophagy

► Phenanthroline induces mitochondrial fragmentation and dysfunctions. ► Phenanthroline induces ATG5 dependent autophagy. ► Phenanthroline induces loss of mitochondrial mass and mitophagy. ► Depletion of Drp1 and ATG5 suppresses Phen-induced loss of mitochondrial mass. Mitochondrial dynamics and mit...

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Bibliographic Details
Published in:FEBS letters 2012-12, Vol.586 (24), p.4303-4310
Main Authors: Park, So Jung, Shin, Ji Hyun, Kim, Eun Sung, Jo, Yoon Kyung, Kim, Jung Ho, Hwang, Jung Jin, Kim, Jin Cheon, Cho, Dong-Hyung
Format: Article
Language:English
Subjects:
Animals
Autophagy
Autophagy-Related Protein 5
Cell Line
Chelating Agents - adverse effects
Down-Regulation - drug effects
Dynamins - metabolism
GTP Phosphohydrolases - metabolism
Humans
Mice
Microtubule-Associated Proteins - metabolism
Mitochondria - drug effects
Mitochondrial Degradation - drug effects
Mitochondrial Dynamics - drug effects
Mitochondrial fission
Mitochondrial Proteins - metabolism
Mitophagy
Phenanthroline
Phenanthrolines - pharmacology
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Summary:► Phenanthroline induces mitochondrial fragmentation and dysfunctions. ► Phenanthroline induces ATG5 dependent autophagy. ► Phenanthroline induces loss of mitochondrial mass and mitophagy. ► Depletion of Drp1 and ATG5 suppresses Phen-induced loss of mitochondrial mass. 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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2012.10.035