Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission-fusion balance within mitochondrial networks.
Mitochondria form interconnected networks that dynamically remodel in response to cellular needs. Using live-cell imaging, we investigate the role of the actin cytoskeleton in regulating mitochondrial fission and fusion. We identify cycling of actin filaments onto and off of subsets of cellular mitochondria. The association of actin filaments with mitochondrial subpopulations is transient; actin quickly disassembles, then reassembles around a distinct subpopulation, efficiently cycling through all cellular mitochondria within 14 min. The focal assembly of actin induces local, Drp1-dependent fragmentation of the mitochondrial network. On actin disassembly, fragmented mitochondria undergo rapid fusion, leading to regional recovery of the tubular mitochondrial network. Cycling requires dynamic actin polymerization and is blocked by inhibitors of both Arp2/3 and formins. We propose that cyclic assembly of actin onto mitochondria modulates the fission/fusion balance, promotes network remodelling and content mixing, and thus may serve as an essential mechanism regulating mitochondrial network homeostasis.
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Andrew S
AS
Moore
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Yvette C
YC
Wong
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.|Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cory L
CL
Simpson
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Erika L F
EL
Holzbaur
J Biol Chem. 2007 Aug 3;282(31):22977-83
17545159
J Biol Chem. 2009 Jun 26;284(26):17783-95
19411255
Curr Opin Cell Biol. 2006 Aug;18(4):453-9
16781135
PLoS One. 2008 Sep 22;3(9):e3257
18806874
Bioarchitecture. 2014;4(6):189-202
26317264
J Cell Sci. 2004 Jun 1;117(Pt 13):2653-62
15138283
Science. 2013 Jan 25;339(6118):464-7
23349293
Cold Spring Harb Perspect Biol. 2013 Apr 01;5(4):a013227
23545422
Nat Rev Mol Cell Biol. 2014 Oct;15(10):634-46
25237825
Dev Cell. 2014 Jul 14;30(1):71-85
25026034
Nat Cell Biol. 2015 Apr;17(4):445-57
25799062
J Biol Chem. 2007 Apr 13;282(15):11521-9
17301055
Ann N Y Acad Sci. 2010 Jul;1201:34-9
20649536
J Cell Biol. 1998 Oct 19;143(2):351-8
9786947
Curr Biol. 2004 Feb 17;14 (4):340-5
14972687
Nat Biotechnol. 2006 Jan;24(1):95-9
16369538
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15927-32
15509649
Nat Methods. 2008 Jul;5(7):605-7
18536722
Ann N Y Acad Sci. 2010 Jul;1201:21-5
20649534
Dev Cell. 2008 Feb;14(2):193-204
18267088
Nature. 2014 Jan 16;505(7483):335-43
24429632
Elife. 2015 Nov 26;4:e11553
26609810
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3162-7
11248049
Curr Biol. 2014 Feb 17;24(4):409-14
24485837
J Cell Biol. 2015 Jan 5;208(1):109-23
25547155
J Cell Sci. 2013 May 15;126(Pt 10):2187-97
23525002
EMBO J. 2008 Jan 23;27(2):433-46
18200046
Methods Mol Biol. 2010;585:127-46
19908001
Science. 2011 Oct 21;334(6054):358-62
21885730
J Cell Sci. 2001 Mar;114(Pt 5):867-74
11181170
J Neurosci. 2008 Aug 13;28(33):8306-15
18701693
Mol Cell. 1999 Nov;4(5):815-26
10619028
Nat Cell Biol. 2011 Aug 07;13(9):1108-15
21822277
Mol Biol Cell. 2013 Mar;24(5):659-67
23283981
Science. 2012 Aug 31;337(6098):1062-5
22936770
Elife. 2015 Aug 25;4:null
26305500
Curr Biol. 2013 Jul 8;23(13):1173-80
23770188