Mitochondrial fragmentation caused by phenanthroline promotes mitophagy

作者:Park So Jung; Shin Ji Hyun; Kim Eun Sung; Jo Yoon Kyung; Kim Jung Ho; Hwang Jung Jin; Kim Jin Cheon; Cho Dong Hyung*
来源:FEBS Letters, 2012, 586(24): 4303-4310.
DOI:10.1016/j.febslet.2012.10.035

摘要

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.

  • 出版日期2012-12-14