Mitochondrial fragmentation caused by phenanthroline promotes mitophagy

被引：55

作者：

Park, So Jung ^{[1
]}

Shin, Ji Hyun ^{[1
]}

Kim, Eun Sung ^{[1
]}

Jo, Yoon Kyung ^{[1
]}

Kim, Jung Ho ^{[1
]}

Hwang, Jung Jin ^{[2
]}

Kim, Jin Cheon ^{[2
,3
]}

Cho, Dong-Hyung ^{[1
]}

机构：

[1] Kyung Hee Univ, Grad Sch EW Med Sci, Yongin 446701, Gyeoggi Do, South Korea

[2] Univ Ulsan, Inst Innovat Canc Res, Coll Med, Asan Med Ctr, Seoul 138736, South Korea

[3] Univ Ulsan, Dept Surg, Coll Med, Asan Med Ctr, Seoul 138736, South Korea

来源：

FEBS LETTERS | 2012年 / 586卷 / 24期

关键词：

Phenanthroline; Mitochondrial fission; Autophagy; Mitophagy; CELL-DEATH; AUTOPHAGY; DISEASE; DYNAMICS; FISSION; OPA1; INCREASES; APOPTOSIS; SCREEN; PARKIN;

D O I：

10.1016/j.febslet.2012.10.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：4303 / 4310

页数：8

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