A Small Molecule Promotes Mitochondrial Fusion in Mammalian Cells

被引：126
作者：
Wang, Danling [1 ]
Wang, Jianing [1 ]
Bonamy, Ghislain M. C. [2 ]
Meeusen, Shelly [2 ]
Brusch, Richard G. [2 ]
Turk, Carolina [2 ]
Yang, Pengyu [1 ]
Schultz, Peter G. [1 ]
机构：
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[2] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2012年 / 51卷 / 37期
关键词：
ATP synthase; drug design; mitochondrial fusion; phenotypic screening; CYTOCHROME-C RELEASE; DISEASE IMPLICATIONS; FISSION; PROTEIN; DYNAMICS; FRAGMENTATION; NEURONS; SIGNALS; PINK1; OUTER;
D O I：
10.1002/anie.201204589
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Mitochondrial dynamics: An image-based screen identified a small molecule, M1, that specifically promotes the fusion of fragmented mitochondria and protects cells from mitochondrial-fragmentation-associated cell death. Mechanistic studies revealed that M1 shifts the mitochondrial dynamic balance towards fusion (see picture). © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
引用
收藏
页码：9302 / 9305
页数：4
相关论文
共 39 条
[1]   Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol [J].
Breckenridge, DG ;
Stojanovic, M ;
Marcellus, RC ;
Shore, GC .
JOURNAL OF CELL BIOLOGY, 2003, 160 (07) :1115-1127
[2]   Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis [J].
Brooks, Craig ;
Cho, Sung-Gyu ;
Wang, Cong-Yi ;
Yang, Tianxin ;
Dong, Zheng .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2011, 300 (03) :C447-C455
[3]   Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization [J].
Cassidy-Stone, Ann ;
Chipuk, Jerry E. ;
Ingerman', Elena ;
Song, Cheng ;
Yoo, Choong ;
Kuwana, Tomomi ;
Kurth, Mark J. ;
Shaw, Jared T. ;
Hinshaw, Jenny E. ;
Green, Douglas R. ;
Nunnari, Jodi .
DEVELOPMENTAL CELL, 2008, 14 (02) :193-204
[4]   Mitochondrial fusion and fission in mammals [J].
Chan, David C. .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2006, 22 :79-99
[5]   Disruption of fusion results in mitochondrial heterogeneity and dysfunction [J].
Chen, HC ;
Chomyn, A ;
Chan, DC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (28) :26185-26192
[6]   Mitochondrial fusion protects against neurodegeneration in the cerebellum [J].
Chen, Hsiuchen ;
McCaffery, J. Michael ;
Chan, David C. .
CELL, 2007, 130 (03) :548-562
[7]   Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis [J].
Estaquier, J. ;
Arnoult, D. .
CELL DEATH AND DIFFERENTIATION, 2007, 14 (06) :1086-1094
[8]   The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis [J].
Frank, S ;
Gaume, B ;
Bergmann-Leitner, ES ;
Leitner, WW ;
Robert, EG ;
Catez, F ;
Smith, CL ;
Youle, RJ .
DEVELOPMENTAL CELL, 2001, 1 (04) :515-525
[9]   CELL-TO-CELL COMMUNICATION AND OVULATION - STUDY OF CUMULUS-OOCYTE COMPLEX [J].
GILULA, NB ;
EPSTEIN, ML ;
BEERS, WH .
JOURNAL OF CELL BIOLOGY, 1978, 78 (01) :58-75
[10]   The machines that divide and fuse mitochondria [J].
Hoppins, Suzanne ;
Lackner, Laura ;
Nunnari, Jodi .
ANNUAL REVIEW OF BIOCHEMISTRY, 2007, 76 :751-780
1234