This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yoon, Y.
Right arrow Articles by McNiven, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yoon, Y.
Right arrow Articles by McNiven, M. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2003, p. 5409-5420, Vol. 23, No. 15
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.15.5409-5420.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Mitochondrial Protein hFis1 Regulates Mitochondrial Fission in Mammalian Cells through an Interaction with the Dynamin-Like Protein DLP1

Yisang Yoon, Eugene W. Krueger, Barbara J. Oswald, and Mark A. McNiven*

Center for Basic Research in Digestive Diseases and Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota 55905

Received 10 May 2002/ Returned for modification 30 July 2002/ Accepted 8 May 2003

The yeast protein Fis1p has been shown to participate in mitochondrial fission mediated by the dynamin-related protein Dnm1p. In mammalian cells, the dynamin-like protein DLP1/Drp1 functions as a mitochondrial fission protein, but the mechanisms by which DLP1/Drp1 and the mitochondrial membrane interact during the fission process are undefined. In this study, we have tested the role of a mammalian homologue of Fis1p, hFis1, and provided new and mechanistic information about the control of mitochondrial fission in mammalian cells. Through differential tagging and deletion experiments, we demonstrate that the intact C-terminal structure of hFis1 is essential for mitochondrial localization, whereas the N-terminal region of hFis1 is necessary for mitochondrial fission. Remarkably, an increased level of cellular hFis1 strongly promotes mitochondrial fission, resulting in an accumulation of fragmented mitochondria. Conversely, cell microinjection of hFis1 antibodies or treatment with hFis1 antisense oligonucleotides induces an elongated and collapsed mitochondrial morphology. Further, fluorescence resonance energy transfer and coimmunoprecipitation studies demonstrate that hFis1 interacts with DLP1. These results suggest that hFis1 participates in mitochondrial fission through an interaction that recruits DLP1 from the cytosol. We propose that hFis1 is a limiting factor in mitochondrial fission and that the number of hFis1 molecules on the mitochondrial surface determines fission frequency.

* Corresponding author. Mailing address: Mayo Clinic, 200 1st St., S.W., Rochester, MN 55905. Phone: (507) 284-0683. Fax: (507) 284-0762. E-mail: mcniven.mark{at}mayo.edu.

Molecular and Cellular Biology, August 2003, p. 5409-5420, Vol. 23, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.15.5409-5420.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Liesa, M., Palacin, M., Zorzano, A. (2009). Mitochondrial Dynamics in Mammalian Health and Disease. Physiol. Rev. 89: 799-845 [Abstract] [Full Text]  
  • Zhao, J., Liu, T., Jin, S.-B., Tomilin, N., Castro, J., Shupliakov, O., Lendahl, U., Nister, M. (2009). The novel conserved mitochondrial inner-membrane protein MTGM regulates mitochondrial morphology and cell proliferation. J. Cell Sci. 122: 2252-2262 [Abstract] [Full Text]  
  • Aihara, T., Nakamura, N., Honda, S., Hirose, S. (2009). A Novel Potential Role for Gametogenetin-Binding Protein 1 (GGNBP1) in Mitochondrial Morphogenesis During Spermatogenesis in Mice. Biol. Reprod. 80: 762-770 [Abstract] [Full Text]  
  • Berman, S. B., Chen, Y.-b., Qi, B., McCaffery, J. M., Rucker, E. B. III, Goebbels, S., Nave, K.-A., Arnold, B. A., Jonas, E. A., Pineda, F. J., Hardwick, J. M. (2009). Bcl-xL increases mitochondrial fission, fusion, and biomass in neurons. JCB 184: 707-719 [Abstract] [Full Text]  
  • Etxebarria, A., Terrones, O., Yamaguchi, H., Landajuela, A., Landeta, O., Antonsson, B., Wang, H.-G., Basanez, G. (2009). Endophilin B1/Bif-1 Stimulates BAX Activation Independently from Its Capacity to Produce Large Scale Membrane Morphological Rearrangements. J. Biol. Chem. 284: 4200-4212 [Abstract] [Full Text]  
  • Park, K.-S., Wiederkehr, A., Kirkpatrick, C., Mattenberger, Y., Martinou, J.-C., Marchetti, P., Demaurex, N., Wollheim, C. B. (2008). Selective Actions of Mitochondrial Fission/Fusion Genes on Metabolism-Secretion Coupling in Insulin-releasing Cells. J. Biol. Chem. 283: 33347-33356 [Abstract] [Full Text]  
  • Delille, H. K., Schrader, M. (2008). Targeting of hFis1 to Peroxisomes Is Mediated by Pex19p. J. Biol. Chem. 283: 31107-31115 [Abstract] [Full Text]  
  • Arnold, S., de Araujo, G. W., Beyer, C. (2008). Gender-specific regulation of mitochondrial fusion and fission gene transcription and viability of cortical astrocytes by steroid hormones. J Mol Endocrinol 41: 289-300 [Abstract] [Full Text]  
  • Zhang, X.-C., Hu, J.-P. (2008). FISSION1A and FISSION1B Proteins Mediate the Fission of Peroxisomes and Mitochondria in Arabidopsis. Mol Plant 1: 1036-1047 [Abstract] [Full Text]  
  • Tan, F. J., Husain, M., Manlandro, C. M., Koppenol, M., Fire, A. Z., Hill, R. B. (2008). CED-9 and mitochondrial homeostasis in C. elegans muscle. J. Cell Sci. 121: 3373-3382 [Abstract] [Full Text]  
  • Han, X.-J., Lu, Y.-F., Li, S.-A., Kaitsuka, T., Sato, Y., Tomizawa, K., Nairn, A. C., Takei, K., Matsui, H., Matsushita, M. (2008). CaM kinase I{alpha}-induced phosphorylation of Drp1 regulates mitochondrial morphology. JCB 182: 573-585 [Abstract] [Full Text]  
  • Yu, T., Sheu, S.-S., Robotham, J. L., Yoon, Y. (2008). Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 79: 341-351 [Abstract] [Full Text]  
  • Suen, D.-F., Norris, K. L., Youle, R. J. (2008). Mitochondrial dynamics and apoptosis. Genes Dev. 22: 1577-1590 [Abstract] [Full Text]  
  • Kemper, C., Habib, S. J., Engl, G., Heckmeyer, P., Dimmer, K. S., Rapaport, D. (2008). Integration of tail-anchored proteins into the mitochondrial outer membrane does not require any known import components. J. Cell Sci. 121: 1990-1998 [Abstract] [Full Text]  
  • Lingard, M. J., Gidda, S. K., Bingham, S., Rothstein, S. J., Mullen, R. T., Trelease, R. N. (2008). Arabidopsis PEROXIN11c-e, FISSION1b, and DYNAMIN-RELATED PROTEIN3A Cooperate in Cell Cycle-Associated Replication of Peroxisomes. Plant Cell 20: 1567-1585 [Abstract] [Full Text]  
  • Gandre-Babbe, S., van der Bliek, A. M. (2008). The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian Cells. Mol. Biol. Cell 19: 2402-2412 [Abstract] [Full Text]  
  • Yang, Y., Ouyang, Y., Yang, L., Beal, M. F., McQuibban, A., Vogel, H., Lu, B. (2008). Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc. Natl. Acad. Sci. USA 105: 7070-7075 [Abstract] [Full Text]  
  • Nakamura, N., Hirose, S. (2008). Regulation of Mitochondrial Morphology by USP30, a Deubiquitinating Enzyme Present in the Mitochondrial Outer Membrane. Mol. Biol. Cell 19: 1903-1911 [Abstract] [Full Text]  
  • Sung, J. Y., Engmann, O., Teylan, M. A., Nairn, A. C., Greengard, P., Kim, Y. (2008). WAVE1 controls neuronal activity-induced mitochondrial distribution in dendritic spines. Proc. Natl. Acad. Sci. USA 105: 3112-3116 [Abstract] [Full Text]  
  • Parra, V., Eisner, V., Chiong, M., Criollo, A., Moraga, F., Garcia, A., Hartel, S., Jaimovich, E., Zorzano, A., Hidalgo, C., Lavandero, S. (2008). Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis. Cardiovasc Res 77: 387-397 [Abstract] [Full Text]  
  • Wells, R. C., Picton, L. K., Williams, S. C. P., Tan, F. J., Hill, R. B. (2007). Direct Binding of the Dynamin-like GTPase, Dnm1, to Mitochondrial Dynamics Protein Fis1 Is Negatively Regulated by the Fis1 N-terminal Arm. J. Biol. Chem. 282: 33769-33775 [Abstract] [Full Text]  
  • Bras, M., Yuste, V. J., Roue, G., Barbier, S., Sancho, P., Virely, C., Rubio, M., Baudet, S., Esquerda, J. E., Merle-Beral, H., Sarfati, M., Susin, S. A. (2007). Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells. Mol. Cell. Biol. 27: 7073-7088 [Abstract] [Full Text]  
  • Karbowski, M., Neutzner, A., Youle, R. J. (2007). The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. JCB 178: 71-84 [Abstract] [Full Text]  
  • Lee, S., Jeong, S.-Y., Lim, W.-C., Kim, S., Park, Y.-Y., Sun, X., Youle, R. J., Cho, H. (2007). Mitochondrial Fission and Fusion Mediators, hFis1 and OPA1, Modulate Cellular Senescence. J. Biol. Chem. 282: 22977-22983 [Abstract] [Full Text]  
  • Mandemakers, W., Morais, V. A., De Strooper, B. (2007). A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases. J. Cell Sci. 120: 1707-1716 [Abstract] [Full Text]  
  • Wasiak, S., Zunino, R., McBride, H. M. (2007). Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. JCB 177: 439-450 [Abstract] [Full Text]  
  • Waterham, H. R., Koster, J., van Roermund, C. W.T., Mooyer, P. A.W., Wanders, R. J.A., Leonard, J. V. (2007). A Lethal Defect of Mitochondrial and Peroxisomal Fission. NEJM 356: 1736-1741 [Abstract] [Full Text]  
  • Taguchi, N., Ishihara, N., Jofuku, A., Oka, T., Mihara, K. (2007). Mitotic Phosphorylation of Dynamin-related GTPase Drp1 Participates in Mitochondrial Fission. J. Biol. Chem. 282: 11521-11529 [Abstract] [Full Text]  
  • Nishida, K., Yagisawa, F., Kuroiwa, H., Yoshida, Y., Kuroiwa, T. (2007). WD40 protein Mda1 is purified with Dnm1 and forms a dividing ring for mitochondria before Dnm1 in Cyanidioschyzon merolae. Proc. Natl. Acad. Sci. USA 104: 4736-4741 [Abstract] [Full Text]  
  • Campello, S., Lacalle, R. A., Bettella, M., Manes, S., Scorrano, L., Viola, A. (2006). Orchestration of lymphocyte chemotaxis by mitochondrial dynamics. JEM 203: 2879-2886 [Abstract] [Full Text]  
  • Jennings, J. J. Jr., Zhu, J.-h., Rbaibi, Y., Luo, X., Chu, C. T., Kiselyov, K. (2006). Mitochondrial Aberrations in Mucolipidosis Type IV. J. Biol. Chem. 281: 39041-39050 [Abstract] [Full Text]  
  • Alirol, E., James, D., Huber, D., Marchetto, A., Vergani, L., Martinou, J.-C., Scorrano, L. (2006). The Mitochondrial Fission Protein hFis1 Requires the Endoplasmic Reticulum Gateway to Induce Apoptosis. Mol. Biol. Cell 17: 4593-4605 [Abstract] [Full Text]  
  • Parone, P. A., James, D. I., Da Cruz, S., Mattenberger, Y., Donze, O., Barja, F., Martinou, J.-C. (2006). Inhibiting the mitochondrial fission machinery does not prevent bax/bak-dependent apoptosis.. Mol. Cell. Biol. 26: 7397-7408 [Abstract] [Full Text]  
  • Kuravi, K., Nagotu, S., Krikken, A. M., Sjollema, K., Deckers, M., Erdmann, R., Veenhuis, M., van der Klei, I. J. (2006). Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae. J. Cell Sci. 119: 3994-4001 [Abstract] [Full Text]  
  • Dimmer, K. S., Scorrano, L. (2006). (De)constructing Mitochondria: What For?. Physiology 21: 233-241 [Abstract] [Full Text]  
  • Scott, I., Tobin, A. K., Logan, D. C. (2006). BIGYIN, an orthologue of human and yeast FIS1 genes functions in the control of mitochondrial size and number in Arabidopsis thaliana. J Exp Bot 57: 1275-1280 [Abstract] [Full Text]  
  • Yu, T., Robotham, J. L., Yoon, Y. (2006). Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc. Natl. Acad. Sci. USA 103: 2653-2658 [Abstract] [Full Text]  
  • Naylor, K., Ingerman, E., Okreglak, V., Marino, M., Hinshaw, J. E., Nunnari, J. (2006). Mdv1 Interacts with Assembled Dnm1 to Promote Mitochondrial Division. J. Biol. Chem. 281: 2177-2183 [Abstract] [Full Text]  
  • Scheckhuber, C. (2005). Mitochondrial Dynamics in Cell Life and Death. Sci Aging Knowl Environ 2005: pe36-pe36 [Abstract] [Full Text]  
  • Koch, A., Yoon, Y., Bonekamp, N. A., McNiven, M. A., Schrader, M. (2005). A Role for Fis1 in Both Mitochondrial and Peroxisomal Fission in Mammalian Cells. Mol. Biol. Cell 16: 5077-5086 [Abstract] [Full Text]  
  • Karren, M. A., Coonrod, E. M., Anderson, T. K., Shaw, J. M. (2005). The role of Fis1p-Mdv1p interactions in mitochondrial fission complex assembly. JCB 171: 291-301 [Abstract] [Full Text]  
  • Chen, H., Chan, D. C. (2005). Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14: R283-R289 [Abstract] [Full Text]  
  • Yu, T., Fox, R. J., Burwell, L. S., Yoon, Y. (2005). Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1. J. Cell Sci. 118: 4141-4151 [Abstract] [Full Text]  
  • Tondera, D., Czauderna, F., Paulick, K., Schwarzer, R., Kaufmann, J., Santel, A. (2005). The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. J. Cell Sci. 118: 3049-3059 [Abstract] [Full Text]  
  • Neuspiel, M., Zunino, R., Gangaraju, S., Rippstein, P., McBride, H. (2005). Activated Mitofusin 2 Signals Mitochondrial Fusion, Interferes with Bax Activation, and Reduces Susceptibility to Radical Induced Depolarization. J. Biol. Chem. 280: 25060-25070 [Abstract] [Full Text]  
  • Suzuki, M., Neutzner, A., Tjandra, N., Youle, R. J. (2005). Novel Structure of the N Terminus in Yeast Fis1 Correlates with a Specialized Function in Mitochondrial Fission. J. Biol. Chem. 280: 21444-21452 [Abstract] [Full Text]  
  • Yoon, Y. (2005). Regulation of Mitochondrial Dynamics: Another Process Modulated by Ca2+ Signals?. Sci Signal 2005: pe18-pe18 [Abstract] [Full Text]  
  • van Herpen, R. E. M. A., Oude Ophuis, R. J. A., Wijers, M., Bennink, M. B., van de Loo, F. A. J., Fransen, J., Wieringa, B., Wansink, D. G. (2005). Divergent Mitochondrial and Endoplasmic Reticulum Association of DMPK Splice Isoforms Depends on Unique Sequence Arrangements in Tail Anchors. Mol. Cell. Biol. 25: 1402-1414 [Abstract] [Full Text]  
  • Pitts, K. R., McNiven, M. A., Yoon, Y. (2004). Mitochondria-specific Function of the Dynamin Family Protein DLP1 Is Mediated by Its C-terminal Domains. J. Biol. Chem. 279: 50286-50294 [Abstract] [Full Text]  
  • Fannjiang, Y., Cheng, W.-C., Lee, S. J., Qi, B., Pevsner, J., McCaffery, J. M., Hill, R. B., Basanez, G., Hardwick, J. M. (2004). Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev. 18: 2785-2797 [Abstract] [Full Text]  
  • Lee, Y.-j., Jeong, S.-Y., Karbowski, M., Smith, C. L., Youle, R. J. (2004). Roles of the Mammalian Mitochondrial Fission and Fusion Mediators Fis1, Drp1, and Opa1 in Apoptosis. Mol. Biol. Cell 15: 5001-5011 [Abstract] [Full Text]  
  • Brookes, P. S., Yoon, Y., Robotham, J. L., Anders, M. W., Sheu, S.-S. (2004). Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am. J. Physiol. Cell Physiol. 287: C817-C833 [Abstract] [Full Text]  
  • Arai, R., Ito, K., Wakiyama, M., Matsumoto, E., Sakamoto, A., Etou, Y., Otsuki, M., Inoue, M., Hayashizaki, Y., Miyagishi, M., Taira, K., Shirouzu, M., Yokoyama, S. (2004). Establishment of Stable hFis1 Knockdown Cells with an siRNA Expression Vector. J Biochem 136: 421-425 [Abstract] [Full Text]  
  • Karbowski, M., Jeong, S.-Y., Youle, R. J. (2004). Endophilin B1 is required for the maintenance of mitochondrial morphology. JCB 166: 1027-1039 [Abstract] [Full Text]  
  • Tondera, D., Santel, A., Schwarzer, R., Dames, S., Giese, K., Klippel, A., Kaufmann, J. (2004). Knockdown of MTP18, a Novel Phosphatidylinositol 3-Kinase-dependent Protein, Affects Mitochondrial Morphology and Induces Apoptosis. J. Biol. Chem. 279: 31544-31555 [Abstract] [Full Text]  
  • Frieden, M., James, D., Castelbou, C., Danckaert, A., Martinou, J.-C., Demaurex, N. (2004). Ca2+ Homeostasis during Mitochondrial Fragmentation and Perinuclear Clustering Induced by hFis1. J. Biol. Chem. 279: 22704-22714 [Abstract] [Full Text]  
  • Stojanovski, D., Koutsopoulos, O. S., Okamoto, K., Ryan, M. T. (2004). Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology. J. Cell Sci. 117: 1201-1210 [Abstract] [Full Text]  
  • Osteryoung, K. W., Nunnari, J. (2003). The Division of Endosymbiotic Organelles. Science 302: 1698-1704 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»