An Actin-Dependent Step in Mitochondrial Fission Mediated by the ER-Associated Formin INF2

被引：639

作者：

Korobova, Farida ^{[1
]}

Ramabhadran, Vinay ^{[2
]}

Higgs, Henry N. ^{[1
]}

机构：

[1] Dartmouth, Geisel Sch Med, Dept Biochem, Hanover, NH 03755 USA

[2] Tufts Univ, Sackler Sch Grad Biomed Sci, Howard Hughes Med Inst, Boston, MA 02111 USA

来源：

SCIENCE | 2013年 / 339卷 / 6118期

基金：

美国国家科学基金会;

关键词：

MARIE-TOOTH-DISEASE; MUTATIONS; PROTEIN; DYNAMICS; POLYMERIZATION; MOVEMENT; FUSION; FAMILY;

D O I：

10.1126/science.1228360

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mitochondrial fission is fundamentally important to cellular physiology. The dynamin-related protein Drp1 mediates fission, and interaction between mitochondrion and endoplasmic reticulum (ER) enhances fission. However, the mechanism for Drp1 recruitment to mitochondria is unclear, although previous results implicate actin involvement. Here, we found that actin polymerization through ER-localized inverted formin 2 (INF2) was required for efficient mitochondrial fission in mammalian cells. INF2 functioned upstream of Drp1. Actin filaments appeared to accumulate between mitochondria and INF2-enriched ER membranes at constriction sites. Thus, INF2-induced actin filaments may drive initial mitochondrial constriction, which allows Drp1-driven secondary constriction. Because INF2 mutations can lead to Charcot-Marie-Tooth disease, our results provide a potential cellular mechanism for this disease state.

引用

页码：464 / 467

页数：4

共 25 条

[1] INF2 Mutations in Charcot-Marie-Tooth Disease with Glomerulopathy [J].

Boyer, Olivia ;

Nevo, Fabien ;

Plaisier, Emmanuelle ;

Funalot, Benoit ;

Gribouval, Olivier ;

Benoit, Genevieve ;

Cong, Evelyne Huynh ;

Arrondel, Christelle ;

Tete, Marie-Josephe ;

Montjean, Rodrick ;

Richard, Laurence ;

Karras, Alexandre ;

Pouteil-Noble, Claire ;

Balafrej, Leila ;

Bonnardeaux, Alain ;

Canaud, Guillaume ;

Charasse, Christophe ;

Dantal, Jacques ;

Deschenes, Georges ;

Deteix, Patrice ;

Dubourg, Odile ;

Petiot, Philippe ;

Pouthier, Dominique ;

Leguern, Eric ;

Guiochon-Mantel, Anne ;

Broutin, Isabelle ;

Gubler, Marie-Claire ;

Saunier, Sophie ;

Ronco, Pierre ;

Vallat, Jean-Michel ;

Angel Alonso, Miguel ;

Antignac, Corinne ;

Mollet, Geraldine .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (25) :2377-2388

[2] Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis [J].

Brown, Elizabeth J. ;

Schloendorff, Johannes S. ;

Becker, Daniel J. ;

Tsukaguchi, Hiroyasu ;

Uscinski, Andrea L. ;

Higgs, Henry N. ;

Henderson, Joel M. ;

Pollak, Martin R. .

NATURE GENETICS, 2010, 42 (01) :72-U91

[3] Role of mitofusin 2 mutations in the physiopathology of Charcot-Marie-Tooth disease type 2A [J].

Cartoni, Romain ;

Martinou, Jean-Claude .

EXPERIMENTAL NEUROLOGY, 2009, 218 (02) :268-273

[4] Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases [J].

Chen, Hsiuchen ;

Chan, David C. .

HUMAN MOLECULAR GENETICS, 2009, 18 :R169-R176

[5] INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization [J].

Chhabra, Ekta Seth ;

Higgs, Henry N. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (36) :26754-26767

[6] INF2 is an endoplasmic reticulum-associated formin protein [J].

Chhabra, Ekta Seth ;

Ramabhadran, Vinay ;

Gerber, Scott A. ;

Higgs, Henry N. .

JOURNAL OF CELL SCIENCE, 2009, 122 (09) :1430-1440

[7]

Correia SC, 2012, ADV EXP MED BIOL, V724, P205, DOI 10.1007/978-1-4614-0653-2_16

[8] Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission [J].

De Vos, KJ ;

Allan, VJ ;

Grierson, AJ ;

Sheetz, MP .

CURRENT BIOLOGY, 2005, 15 (07) :678-683

[9] Tau Promotes Neurodegeneration via DRP1 Mislocalization In Vivo [J].

DuBoff, Brian ;

Goetz, Juergen ;

Feany, Mel B. .

NEURON, 2012, 75 (04) :618-632

[10] Recent advances into the understanding of mitochondrial fission [J].

Elgass, Kirstin ;

Pakay, Julian ;

Ryan, Michael T. ;

Palmer, Catherine S. .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2013, 1833 (01) :150-161

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