![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on December 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 10, 2002
Revised on August 7, 2002
Accepted on August 23, 2002
1 INSERM U 523-Institut de Myologie, Groupe hospitalier Pitie-Salpetriere, 75651 Paris cedex 13, France
* Corresponding author. E-mail address: m.rojo{at}myologie.chups.jussieu.fr.
Mitochondrial fusion remains a largely unknown process despite its observation by live microscopy and the identification of few implicated proteins. Using green and red fluorescent proteins targeted to the mitochondrial matrix, we show that mitochondrial fusion in human cells is efficient and achieves complete mixing of matrix contents within twelve hours. This process is maintained in the absence of a functional respiratory chain, despite disruption of microtubules or after significant reduction of cellular ATP-levels. In contrast, mitochondrial fusion is completely inhibited by protonophores that dissipate the inner membrane potential. This inhibition, which results in rapid fragmentation of mitochondrial filaments, is reversible: small and punctate mitochondria fuse to reform elongated and interconnected ones upon withdrawal of protonophores. Expression of wild type or dominant-negative Drp1 showed that fragmentation is due to Drp1-mediated mitochondrial division. On the other hand, expression of mitofusin 1 (Mfn1), one of the human Fzo-homologs, increased mitochondrial length and interconnectivity. This process, but not Mfn1-targeting, was dependent on the inner membrane potential, indicating that overexpressed Mfn1 stimulates fusion. These results show that human mitochondria represent a single cellular compartment whose exchanges and interconnectivity are dynamically regulated by the balance between continuous fusion and fission reactions.
This article has been cited by other articles:
|
|
 |
|
  D. Narendra, A. Tanaka, D.-F. Suen, and R. J. Youle Parkin is recruited selectively to impaired mitochondria and promotes their autophagy J. Cell Biol., December 1, 2008; 183(5): 795 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Reyes and V. Parpura Mitochondria Modulate Ca2+-Dependent Glutamate Release from Rat Cortical Astrocytes J. Neurosci., September 24, 2008; 28(39): 9682 - 9691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Poole, R. E. Thomas, L. A. Andrews, H. M. McBride, A. J. Whitworth, and L. J. Pallanck The PINK1/Parkin pathway regulates mitochondrial morphology PNAS, February 5, 2008; 105(5): 1638 - 1643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Q. Kwong, M. S. Henning, A. A. Starkov, and G. Manfredi The mitochondrial respiratory chain is a modulator of apoptosis J. Cell Biol., December 17, 2007; 179(6): 1163 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lee, S.-Y. Jeong, W.-C. Lim, S. Kim, Y.-Y. Park, X. Sun, R. J. Youle, and H. Cho Mitochondrial Fission and Fusion Mediators, hFis1 and OPA1, Modulate Cellular Senescence J. Biol. Chem., August 3, 2007; 282(31): 22977 - 22983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wasiak, R. Zunino, and H. M. McBride Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death J. Cell Biol., May 7, 2007; 177(3): 439 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Benard, N. Bellance, D. James, P. Parrone, H. Fernandez, T. Letellier, and R. Rossignol Mitochondrial bioenergetics and structural network organization J. Cell Sci., March 1, 2007; 120(5): 838 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Duvezin-Caubet, R. Jagasia, J. Wagener, S. Hofmann, A. Trifunovic, A. Hansson, A. Chomyn, M. F. Bauer, G. Attardi, N.-G. Larsson, et al. Proteolytic Processing of OPA1 Links Mitochondrial Dysfunction to Alterations in Mitochondrial Morphology J. Biol. Chem., December 8, 2006; 281(49): 37972 - 37979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Alirol, D. James, D. Huber, A. Marchetto, L. Vergani, J.-C. Martinou, and L. Scorrano The Mitochondrial Fission Protein hFis1 Requires the Endoplasmic Reticulum Gateway to Induce Apoptosis Mol. Biol. Cell, November 1, 2006; 17(11): 4593 - 4605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Poncet, A.-L. Pauleau, G. Szabadkai, A. Vozza, S. R. Scholz, M. Le Bras, J.-J. Briere, A. Jalil, R. Le Moigne, C. Brenner, et al. Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA J. Cell Biol., September 25, 2006; 174(7): 985 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Dimmer and L. Scorrano (De)constructing Mitochondria: What For? Physiology, August 1, 2006; 21: 233 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Jonas BCL-xL Regulates Synaptic Plasticity Mol. Interv., August 1, 2006; 6(4): 208 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D'Aurelio, C. D. Gajewski, G. Lenaz, and G. Manfredi Respiratory chain supercomplexes set the threshold for respiration defects in human mtDNA mutant cybrids Hum. Mol. Genet., July 1, 2006; 15(13): 2157 - 2169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bornhovd, F. Vogel, W. Neupert, and A. S. Reichert Mitochondrial Membrane Potential Is Dependent on the Oligomeric State of F1F0-ATP Synthase Supracomplexes J. Biol. Chem., May 19, 2006; 281(20): 13990 - 13998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Frieden, S. Arnaudeau, C. Castelbou, and N. Demaurex Subplasmalemmal Mitochondria Modulate the Activity of Plasma Membrane Ca2+-ATPases J. Biol. Chem., December 30, 2005; 280(52): 43198 - 43208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chen and D. C. Chan Emerging functions of mammalian mitochondrial fusion and fission Hum. Mol. Genet., October 15, 2005; 14(suppl_2): R283 - R289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Niemann, M. Ruegg, V. La Padula, A. Schenone, and U. Suter Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease J. Cell Biol., September 26, 2005; 170(7): 1067 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Honda, T. Aihara, M. Hontani, K. Okubo, and S. Hirose Mutational analysis of action of mitochondrial fusion factor mitofusin-2 J. Cell Sci., July 15, 2005; 118(14): 3153 - 3161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Neuspiel, R. Zunino, S. Gangaraju, P. Rippstein, and H. McBride Activated Mitofusin 2 Signals Mitochondrial Fusion, Interferes with Bax Activation, and Reduces Susceptibility to Radical Induced Depolarization J. Biol. Chem., July 1, 2005; 280(26): 25060 - 25070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Tsaousis, D. P. Martin, E. D. Ladoukakis, D. Posada, and E. Zouros Widespread Recombination in Published Animal mtDNA Sequences Mol. Biol. Evol., April 1, 2005; 22(4): 925 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garnier, D. Fortin, J. Zoll, B. N'Guessan, B. Mettauer, E. Lampert, V. Veksler, and R. Ventura-Clapier Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle FASEB J, January 1, 2005; 19(1): 43 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D'Aurelio, C. D. Gajewski, M. T. Lin, W. M. Mauck, L. Z. Shao, G. Lenaz, C. T. Moraes, and G. Manfredi Heterologous mitochondrial DNA recombination in human cells Hum. Mol. Genet., December 15, 2004; 13(24): 3171 - 3179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ishihara, Y. Eura, and K. Mihara Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity J. Cell Sci., December 15, 2004; 117(26): 6535 - 6546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Fannjiang, W.-C. Cheng, S. J. Lee, B. Qi, J. Pevsner, J. M. McCaffery, R. B. Hill, G. Basanez, and J. M. Hardwick Mitochondrial fission proteins regulate programmed cell death in yeast Genes & Dev., November 15, 2004; 18(22): 2785 - 2797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cipolat, O. M. de Brito, B. Dal Zilio, and L. Scorrano OPA1 requires mitofusin 1 to promote mitochondrial fusion PNAS, November 9, 2004; 101(45): 15927 - 15932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Brookes, Y. Yoon, J. L. Robotham, M. W. Anders, and S.-S. Sheu Calcium, ATP, and ROS: a mitochondrial love-hate triangle Am J Physiol Cell Physiol, October 1, 2004; 287(4): C817 - C833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Karbowski, S.-Y. Jeong, and R. J. Youle Endophilin B1 is required for the maintenance of mitochondrial morphology J. Cell Biol., September 27, 2004; 166(7): 1027 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Meeusen, J. M. McCaffery, and J. Nunnari Mitochondrial Fusion Intermediates Revealed in Vitro Science, September 17, 2004; 305(5691): 1747 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Varadi, L. I. Johnson-Cadwell, V. Cirulli, Y. Yoon, V. J. Allan, and G. A. Rutter Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1 J. Cell Sci., September 1, 2004; 117(19): 4389 - 4400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Koshiba, S. A. Detmer, J. T. Kaiser, H. Chen, J. M. McCaffery, and D. C. Chan Structural Basis of Mitochondrial Tethering by Mitofusin Complexes Science, August 6, 2004; 305(5685): 858 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Legros, F. Malka, P. Frachon, A. Lombes, and M. Rojo Organization and dynamics of human mitochondrial DNA J. Cell Sci., June 1, 2004; 117(13): 2653 - 2662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Karbowski, D. Arnoult, H. Chen, D. C. Chan, C. L. Smith, and R. J. Youle Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis J. Cell Biol., February 16, 2004; 164(4): 493 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Serero, C. Giglione, A. Sardini, J. Martinez-Sanz, and T. Meinnel An Unusual Peptide Deformylase Features in the Human Mitochondrial N-terminal Methionine Excision Pathway J. Biol. Chem., December 26, 2003; 278(52): 52953 - 52963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Eura, N. Ishihara, S. Yokota, and K. Mihara Two Mitofusin Proteins, Mammalian Homologues of FZO, with Distinct Functions Are Both Required for Mitochondrial Fusion J. Biochem., September 1, 2003; 134(3): 333 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Santel, S. Frank, B. Gaume, M. Herrler, R. J. Youle, and M. T. Fuller Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells J. Cell Sci., July 1, 2003; 116(13): 2763 - 2774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olichon, L. Baricault, N. Gas, E. Guillou, A. Valette, P. Belenguer, and G. Lenaers Loss of OPA1 Perturbates the Mitochondrial Inner Membrane Structure and Integrity, Leading to Cytochrome c Release and Apoptosis J. Biol. Chem., February 28, 2003; 278(10): 7743 - 7746. [Abstract] [Full Text] [PDF]
|
|
