Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity
Abstract
The mammalian homologues of yeast and Drosophila Fzo, mitofusin (Mfn) 1 and 2, are both essential for mitochondrial fusion and maintenance of mitochondrial morphology. Though the GTPase domain is required for Mfn protein function, the molecular mechanisms of the GTPase-dependent reaction as well as the functional division of the two Mfn proteins are unknown. To examine the function of Mfn proteins, tethering of mitochondrial membranes was measured in vitro by fluorescence microscopy using green fluorescence protein- or red fluorescent protein-tagged and Mfn1-expressing mitochondria, or by immunoprecipitation using mitochondria harboring HA- or FLAG-tagged Mfn proteins. These experiments revealed that Mfn1-harboring mitochondria were efficiently tethered in a GTP-dependent manner, whereas Mfn2-harboring mitochondria were tethered with only low efficiency. Sucrose density gradient centrifugation followed by co-immunoprecipitation revealed that Mfn1 produced oligomerized ∼250 kDa and ∼450 kDa complexes in a GTP-dependent manner. The ∼450 kDa complex contained oligomerized Mfn1 from distinct apposing membranes (docking complex), whereas the ∼250 kDa complex was composed of Mfn1 present on the same membrane or in the membrane-solubilized state (cis complex). These results were also confirmed using blue-native PAGE. Mfn1 exhibited higher activity for this reaction than Mfn2. Purified recombinant Mfn1 exhibited ∼eightfold higher GTPase activity than Mfn2. These findings indicate that the two Mfn proteins have distinct activities, and suggest that Mfn1 is mainly responsible for GTP-dependent membrane tethering.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
GTP hydrolysis of MFN1 causes a conformational change that allows the OMMs of opposing mitochondria to contact and fuse.
“GTP hydrolysis of MFN1 causes a conformational change that allows the OMMs of opposing mitochondria to contact and fuse [61, 62].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [61]
MFN1 has greater GTPase membrane tethering activity than MFN2, explaining why MFN1 loss causes more fragmentation.
“This difference can be explained because MFN1 has a greater GTPase membrane tethering activity [61].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [61]
Mfn1 and Mfn2 possess several distinct properties, suggesting that they fulfill different roles in fusion.
“Despite some redundancies in their function, the two proteins possess several distinct properties, suggesting that they fulfill different roles in fusion (de Brito and Scorrano, 2008; Eura et al., 2003; Ishihara et al., 2004).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Ishihara et al., 2004
Mitochondrial fusion involves multiple steps, including mitochondrial tethering and fusion of MOMs, docking and fusion of the mitochondrial inner membranes (MIMs) and mixing of intramitochondrial components.
“Mitochondrial fusion involves multiple steps, including mitochondrial tethering and fusion of MOMs, docking and fusion of the mitochondrial inner membranes (MIMs) and mixing of intramitochondrial components (Ishihara et al., 2004).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Ishihara et al., 2004
Cites
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601 · see citing works
The Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis
Frank, S., Gaume, B., Bergmann-Leitner, E. S., Leitner, W. W., Robert, E. G., Catez, F., Smith, C. L., & Youle, R. J. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00055-7 · Cited by 1,755 · see citing works
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A
Züchner, S., Mersiyanova, I. V., Muglia, M., Bissar-Tadmouri, N., Rochelle, J., Dadali, E. L., Zappia, M., Nelis, E., Patitucci, A., Senderek, J., et al. (2004) · Nature Genetics · doi:10.1038/ng1341 · Cited by 1,572 · see citing works
SNARE-mediated membrane fusion
Chen, Y. A., & Scheller, R. H. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052017 · Cited by 1,133 · see citing works
Control of mitochondrial morphology by a human mitofusin
Santel, A., & Fuller, M. T. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.5.867 · Cited by 1,012 · see citing works
Structural Basis of Mitochondrial Tethering by Mitofusin Complexes
Koshiba, T., Detmer, S. A., Kaiser, J. T., Chen, H., McCaffery, J. M., & Chan, D. C. (2004) · Science · doi:10.1126/science.1099793 · Cited by 910 · see citing works
The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast
Bleazard, W., McCaffery, J. M., King, E. J., Bale, S., Mozdy, A. D., Tieu, Q., Nunnari, J. M., & Shaw, J. M. (1999) · Nature Cell Biology · doi:10.1038/13014 · Cited by 795 · see citing works
Dynamics of mitochondrial morphology in healthy cells and during apoptosis
Karbowski, M., & Youle, R. J. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401260 · Cited by 759 · see citing works
Legros, F., Lombès, A., Frachon, P., & Rojo, M. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-06-0330 · Cited by 676 · see citing works
Developmentally Regulated Mitochondrial Fusion Mediated by a Conserved, Novel, Predicted GTPase
Hales, K. G., & Fuller, M. T. (1997) · Cell · doi:10.1016/s0092-8674(00)80319-0 · Cited by 611 · see citing works
Mitochondrial Fusion in Yeast Requires the Transmembrane GTPase Fzo1p
Hermann, G. J., Thatcher, J., Mills, J. P., Hales, K. G., Fuller, M., Nunnari, J., & Shaw, J. (1998) · Journal of Cell Biology · doi:10.1083/jcb.143.2.359 · Cited by 572 · see citing works
Rojo, M., Legros, F., Chateau, D., & Lombès, A. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.8.1663 · Cited by 555 · see citing works
Division versus Fusion: Dnm1p and Fzo1p Antagonistically Regulate Mitochondrial Shape
Sesaki, H., & Jensen, R. E. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.4.699 · Cited by 531 · see citing works
Nunnari, J. M., Marshall, W. F., Straight, A. F., Murray, A., Sedat, J. W., & Walter, P. (1997) · Molecular Biology of the Cell · doi:10.1091/mbc.8.7.1233 · Cited by 514 · see citing works
The Machinery of Mitochondrial Inheritance and Behavior
Yaffe, M. P. (1999) · Science · doi:10.1126/science.283.5407.1493 · Cited by 496 · see citing works
Mitochondrial Fusion Intermediates Revealed in Vitro
Meeusen, S. L., McCaffery, J., & Nunnari, J. (2004) · Science · doi:10.1126/science.1100612 · Cited by 466 · see citing works
Eura, Y. (2003) · Journal of Biochemistry · doi:10.1093/jb/mvg150 · Cited by 445 · cited 19× · see citing works
“Mfn1 and Mfn2 are both essential for mitochondrial fusion reactions, because mitochondria depleted of either Mfn protein fail to fuse after the cell fusion reaction (Chen et al., 2003; Eura et al., 2003).”
BackgroundMethodResultInfluentialSelf-citationMitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells
Santel, A., Frank, S., Gaume, B. R., Herrler, M., Youle, R. J., & Fuller, M. T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00479 · Cited by 445 · see citing works
Mitochondrial dynamics and division in budding yeast
Shaw, J. M., & Nunnari, J. (2002) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)02246-2 · Cited by 375 · see citing works
Rapaport, D., Brunner, M., Neupert, W., & Westermann, B. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.20150 · Cited by 370 · see citing works
Dynamin Self-assembly Stimulates Its GTPase Activity
Warnock, D. E., Hinshaw, J. E., & Schmid, S. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.37.22310 · Cited by 264 · see citing works
Ishihara, N., Jofuku, A., Eura, Y., & Mihara, K. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00050-0 · Cited by 255 · see citing works
Self-citationMitochondrial Dynamics in Mammals
Chen, H., & Chan, D. C. (2004) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(04)59005-1 · Cited by 180 · see citing works
Connection of the Mitochondrial Outer and Inner Membranes by Fzo1 Is Critical for Organellar Fusion
Fritz, S., Rapaport, D., Klanner, E., Neupert, W., & Westermann, B. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.683 · Cited by 156 · see citing works
The Many Shapes of Mitochondrial Membranes
Griparić, L., & van der Bliek, A. M. (2001) · Traffic · doi:10.1034/j.1600-0854.2001.1r008.x · Cited by 145 · see citing works
Yeast mitochondrial dynamics: Fusion, division, segregation, and shape
Jensen, R. E., Hobbs, A. E. A., Cerveny, K. L., & Sesaki, H. (2000) · Microscopy Research and Technique · doi:10.1002/1097-0029(20001215)51:6 · Cited by 134 · see citing works
A fuzzy mitochondrial fusion apparatus comes into focus
Mozdy, A. D., & Shaw, J. M. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1125 · Cited by 130 · see citing works
Suzuki, H., Maeda, M., & Mihara, K. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.9.1895 · Cited by 73 · see citing works
Self-citationScott, S. V., Cassidy-Stone, A., Meeusen, S., & Nunnari, J. M. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00070-x · Cited by 68 · see citing works
Interaction of mitochondria with microtubules in the filamentous fungus Neurospora crassa
Fuchs, F., Prokisch, H., Neupert, W., & Westermann, B. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.9.1931 · Cited by 66 · see citing works
Westermann, B. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(03)00091-0 · Cited by 55 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442 · see citing works
Mitochondria: More Than Just a Powerhouse
McBride, H. M., Neuspiel, M., & Wasiak, S. (2006) · Current Biology · doi:10.1016/j.cub.2006.06.054 · Cited by 1,985 · see citing works
OPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial Fusion
Frezza, C., Cipolat, S., Martins de Brito, O., Micaroni, M., Beznoussenko, G. V., Rudka, T., Bartoli, D., Polishuck, R. S., Danial, N. N., De Strooper, B., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.025 · Cited by 1,673 · see citing works
The cell biology of mitochondrial membrane dynamics
Giacomello, M., Pyakurel, A., Glytsou, C., & Scorrano, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0210-7 · Cited by 1,550 · see citing works
Mitochondrial dynamics: overview of molecular mechanisms
Tilokani, L., Nagashima, S., Paupe, V., & Prudent, J. (2018) · Essays in Biochemistry · doi:10.1042/ebc20170104 · Cited by 1,397 · see citing works
Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction
Chen, H., Chomyn, A., & Chan, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503062200 · Cited by 1,376 · see citing works
Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357 · see citing works
Mitochondrial dynamics and apoptosis
Suen, D.-F., Norris, K. L., & Youle, R. J. (2008) · Genes & Development · doi:10.1101/gad.1658508 · Cited by 1,270 · see citing works
Cassidy-Stone, A., Chipuk, J. E., Ingerman, E., Song, C., Yoo, C., Kuwana, T., Kurth, M. J., Shaw, J. T., Hinshaw, J. E., Green, D. R., et al. (2008) · Developmental Cell · doi:10.1016/j.devcel.2007.11.019 · Cited by 1,200 · see citing works
Rambold, A. S., Kostelecky, B., Elia, N., & Lippincott‐Schwartz, J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1107402108 · Cited by 1,144 · see citing works
BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis
McArthur, K., Whitehead, L. W., Heddleston, J. M., Li, L., Padman, B. S., Oorschot, V., Geoghegan, N. D., Chappaz, S., Davidson, S., San Chin, H., et al. (2018) · Science · doi:10.1126/science.aao6047 · Cited by 1,072 · see citing works
Mitochondrial fragmentation in neurodegeneration.
Knott, A. B., Perkins, G., Schwarzenbacher, R., & Bossy-Wetzel, E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2417 · Cited by 1,002 · see citing works
Mitochondrial Fusion and Fission in Mammals
Chan, D. C. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104638 · Cited by 972 · see citing works
Mitochondrial Dynamics in Mammalian Health and Disease
Liesa, M., Palacín, M., & Zorzano, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00030.2008 · Cited by 953 · see citing works
Regulation of mitochondrial morphology through proteolytic cleavage of OPA1
Ishihara, N., Fujita, Y., Oka, T., & Mihara, K. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601184 · Cited by 899 · see citing works
Self-citationPernas, L. F., & Scorrano, L. (2015) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105011 · Cited by 814 · see citing works
The Machines that Divide and Fuse Mitochondria
Hoppins, S., Lackner, L., & Nunnari, J. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.071905.090048 · Cited by 790 · see citing works
Mitochondrial fission in apoptosis
Youle, R. J., & Karbowski, M. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1697 · Cited by 773 · see citing works
The role of mitochondria in apoptosis
Jeong, S., & Seol, D. (2008) · BMB Reports · doi:10.5483/bmbrep.2008.41.1.011 · Cited by 767 · see citing works
Mitochondrial dynamics regulates migration and invasion of breast cancer cells
Zhao, J., Zhang, J., Yu, M., Xie, Y., Huang, Y., Wolff, D. W., Abel, P. W., & Tu, Y. (2012) · Oncogene · doi:10.1038/onc.2012.494 · Cited by 763 · see citing works
Mitochondrial Morphology and Dynamics in Yeast and Multicellular Eukaryotes
Okamoto, K., & Shaw, J. M. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.093019 · Cited by 737 · see citing works
Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease
Yan, M. H., Wang, X., & Zhu, X. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.014 · Cited by 718 · see citing works
Misko, A. L., Jiang, S., Wegorzewska, I., Milbrandt, J., & Baloh, R. H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.6248-09.2010 · Cited by 643 · see citing works
The mitochondrial pathways of apoptosis
Estaquier, J., Vallette, F., Vayssiere, J.-L., & Mignotte, B. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2869-1_7 · Cited by 637 · see citing works
Role of Bax and Bak in mitochondrial morphogenesis
Karbowski, M., Norris, K. L., Cleland, M. M., Jeong, S.-Y., & Youle, R. J. (2006) · Nature · doi:10.1038/nature05111 · Cited by 625 · see citing works
New insights into the role of mitochondria in aging: mitochondrial dynamics and more
Seo, A. Y., Joseph, A.-M., Dutta, D., Hwang, J. C. Y., Aris, J. P., & Leeuwenburgh, C. (2010) · Journal of Cell Science · doi:10.1242/jcs.070490 · Cited by 522 · see citing works
Mitofusins, from Mitochondria to Metabolism
Schrepfer, E., & Scorrano, L. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.022 · Cited by 490 · see citing works
Terman, A., Kurz, T., Navratil, M., Arriaga, E. A., & Brunk, U. T. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2598 · Cited by 490 · see citing works
A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis
Choi, S., Huang, P., Jenkins, G. M., Chan, D. C., Schiller, J., & Frohman, M. A. (2006) · Nature Cell Biology · doi:10.1038/ncb1487 · Cited by 480 · see citing works
Mitochondrial Inner-Membrane Fusion and Crista Maintenance Requires the Dynamin-Related GTPase Mgm1
Meeusen, S., DeVay, R. M., Block, J., Cassidy-Stone, A., Wayson, S. M., McCaffery, J. M., & Nunnari, J. M. (2006) · Cell · doi:10.1016/j.cell.2006.09.021 · Cited by 474 · see citing works
Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin
Orso, G., Pendin, D., Liu, S., Tosetto, J., Moss, T. J., Faust, J. E., Micaroni, M., Egorova, A., Martinuzzi, A., McNew, J. A., et al. (2009) · Nature · doi:10.1038/nature08280 · Cited by 473 · see citing works
Baloh, R., Schmidt, R., Pestronk, A., & Milbrandt, J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4798-06.2007 · Cited by 471 · see citing works
Quality control of the mitochondrion
Ng, M. Y. W., Wai, T., & Simonsen, A. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.02.009 · Cited by 453 · see citing works
Mfn2 modulates the UPR and mitochondrial function via repression of PERK
Muñoz, J. P., Ivanova, S., Sánchez‐Wandelmer, J., Martínez‐Cristóbal, P., Noguera, E., Sancho, A., Díaz‐Ramos, A., Hernández‐Alvarez, M. I., Sebastián, D., Mauvezin, C., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.168 · Cited by 451 · see citing works
Organization and Function of Membrane Contact Sites
Helle, S. C. J., Kanfer, G., Kolar, K., Lang, A., Michel, A. H., & Kornmann, B. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.01.028 · Cited by 453 · see citing works
Mitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434 · see citing works
OPA1 processing in cell death and disease – the long and short of it
MacVicar, T., & Langer, T. (2016) · Journal of Cell Science · doi:10.1242/jcs.159186 · Cited by 420 · see citing works
Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin
Ban, T., Ishihara, T., Kohno, H., Saita, S., Ichimura, A., Maenaka, K., Oka, T., Mihara, K., & Ishihara, N. (2017) · Nature Cell Biology · doi:10.1038/ncb3560 · Cited by 410 · see citing works
Self-citationMARCH‐V is a novel mitofusin 2‐ and Drp1‐binding protein able to change mitochondrial morphology
Nakamura, N., Kimura, Y. N., Tokuda, M., Honda, S., & Hirose, S. (2006) · EMBO Reports · doi:10.1038/sj.embor.7400790 · Cited by 419 · see citing works
Molecular mechanisms of mitochondrial dynamics
Tábara, L. C., Segawa, M., & Prudent, J. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00785-1 · Cited by 431 · see citing works
Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology
Zhan, M., Brooks, C. R., Liu, F., Sun, L., & Dong, Z. (2013) · Kidney International · doi:10.1038/ki.2012.441 · Cited by 396 · see citing works
Mitochondrial Fusion: The Machineries In and Out
Gao, S., & Hu, J. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.09.008 · Cited by 396 · see citing works
McLelland, G., Goiran, T., Yi, W., Dorval, G., Chen, C. X., Lauinger, N. D., Krahn, A. I., Valimehr, S., Raković, A., Rouiller, I., et al. (2018) · eLife · doi:10.7554/elife.32866 · Cited by 386 · see citing works
Papanicolaou, K. N., Khairallah, R. J., Ngoh, G. A., Chikando, A. C., Luptak, I., O’Shea, K. M., Riley, D. D., Lugus, J. J., Colucci, W. S., Lederer, W. J., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.00911-10 · Cited by 358 · see citing works
Mitofusin 2: from functions to disease
Filadi, R., Pendin, D., & Pizzo, P. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0023-6 · Cited by 359 · see citing works
Determinants and outcomes of mitochondrial dynamics
Quintana–Cabrera, R., & Scorrano, L. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.02.012 · Cited by 345 · see citing works
Detmer, S. A., & Chan, D. C. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200611080 · Cited by 343 · see citing works
Shai, N., Yifrach, E., van Roermund, C. W. T., Cohen, N., Bibi, C., IJlst, L., Cavellini, L., Meurisse, J., Schuster, R., Zada, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03957-8 · Cited by 320 · see citing works
Leboucher, G. P., Tsai, Y. C., Yang, M., Shaw, K. C., Zhou, M., Veenstra, T. D., Glickman, M. H., & Weissman, A. M. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.041 · Cited by 334 · see citing works
MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion
Cao, Y.-L., Meng, S., Chen, Y., Feng, J.-X., Gu, D.-D., Yu, B., Li, Y.-J., Yang, J.-Y., Liao, S., Chan, D. C., et al. (2017) · Nature · doi:10.1038/nature21077 · Cited by 326 · see citing works
Mitochondrial morphology and cardiovascular disease
Ong, S., & Hausenloy, D. J. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq237 · Cited by 325 · see citing works
Mitochondrial morphology transitions and functions: implications for retrograde signaling?
Picard, M. A., Shirihai, O. S., Gentil, B. J., & Burelle, Y. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00584.2012 · Cited by 320 · see citing works
Determinants and Functions of Mitochondrial Behavior
Labbè, K., Murley, A., & Nunnari, J. M. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155756 · Cited by 315 · see citing works
The Metabolic Theory of Pulmonary Arterial Hypertension
Paulin, R., & Michelakis, E. D. (2014) · Circulation Research · doi:10.1161/circresaha.115.301130 · Cited by 317 · see citing works
Neuspiel, M., Zunino, R., Gangaraju, S., Rippstein, P. U., & McBride, H. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501599200 · Cited by 308 · see citing works
Dietrich, M. O., Liu, Z.-W., & Horvath, T. L. (2013) · Cell · doi:10.1016/j.cell.2013.09.004 · Cited by 306 · see citing works
MITOL Regulates Endoplasmic Reticulum-Mitochondria Contacts via Mitofusin2
Sugiura, A., Nagashima, S., Tokuyama, T., Amo, T., Matsuki, Y., Ishido, S., Kudo, Y., McBride, H. M., Fukuda, T., Matsushita, N., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.04.023 · Cited by 303 · see citing works
An intimate liaison: spatial organization of the endoplasmic reticulum–mitochondria relationship
de Brito, O. M., & Scorrano, L. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.177 · Cited by 297 · see citing works
Abnormal mitochondrial dynamics and neurodegenerative diseases
Su, B., Wang, X., Zheng, L., Perry, G. L., Smith, M. A., & Zhu, X. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.09.013 · Cited by 289 · see citing works
Hall, A. R., Burke, N., Dongworth, R. K., & Hausenloy, D. J. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12516 · Cited by 288 · see citing works
The regulation of mitochondrial morphology: Intricate mechanisms and dynamic machinery
Palmer, C. S., Osellame, L. D., Stojanovski, D., & Ryan, M. T. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.05.021 · Cited by 280 · see citing works
The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease
Wang, X., Su, B., Zheng, L., Perry, G. L., Smith, M. A., & Zhu, X. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05867.x · Cited by 278 · see citing works
Hydrogen sulfide signaling in mitochondria and disease
Murphy, B., Bhattacharya, R., & Mukherjee, P. (2019) · The FASEB Journal · doi:10.1096/fj.201901304r · Cited by 279 · see citing works
Alqahtani, T., Deore, S. L., Kide, A. A., Shende, B. A., Sharma, R., Chakole, R. D., Nemade, L. S., Kale, N. K., Borah, S., Deokar, S. S., et al. (2023) · Mitochondrion · doi:10.1016/j.mito.2023.05.007 · Cited by 289 · see citing works
Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion
DeVay, R. M., Domínguez‐Ramírez, L., Lackner, L. L., Hoppins, S. C., Stahlberg, H., & Nunnari, J. M. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200906098 · Cited by 276 · see citing works
Mutant huntingtin and mitochondrial dysfunction
Bossy‐Wetzel, E., Petrilli, A. M., & Knott, A. B. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.09.004 · Cited by 269 · see citing works
The SUMO protease SENP5 is required to maintain mitochondrial morphology and function
Zunino, R., Schauss, A. C., Rippstein, P. U., Andrade-Navarro, M. A., & McBride, H. M. (2007) · Journal of Cell Science · doi:10.1242/jcs.03418 · Cited by 262 · see citing works
Stephan, T., Brüser, C., Deckers, M., Steyer, A. M., Balzarotti, F., Barbot, M., Behr, T. S., Heim, G., Hübner, W., Ilgen, P., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019104105 · Cited by 253 · see citing works
Recent advances into the understanding of mitochondrial fission
Elgass, K., Pakay, J. L., Ryan, M. T., & Palmer, C. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.05.002 · Cited by 262 · see citing works
Regulation of mitochondrial fusion and division
Cerveny, K. L., Tamura, Y., Zhang, Z., Jensen, R. E., & Sesaki, H. (2007) · Trends in Cell Biology · doi:10.1016/j.tcb.2007.08.006 · Cited by 261 · see citing works
Nicotinamide-induced Mitophagy
Jang, S., Kang, H. T., & Hwang, E. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.363747 · Cited by 259 · see citing works
Quality Control of Mitochondrial ProteostasisPreprint
Baker, M. J., Tatsuta, T., & Langer, T. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007559 · Cited by 260 · see citing works
Molecular mechanisms and physiologic functions of mitochondrial dynamics
Otera, H., & Mihara, K. (2011) · The Journal of Biochemistry · doi:10.1093/jb/mvr002 · Cited by 251 · see citing works
Self-citationImpairing the Mitochondrial Fission and Fusion Balance: A New Mechanism of Neurodegeneration
Knott, A. B., & Bossy‐Wetzel, E. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.030 · Cited by 258 · see citing works
Molecular Machinery of Mitochondrial Fusion and Fission
Westermann, B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800011200 · Cited by 251 · see citing works
Abnormalities of Mitochondrial Dynamics in Neurodegenerative Diseases
Gao, J., Wang, L., Liu, J., Xie, F., Su, B., & Wang, X. (2017) · Antioxidants · doi:10.3390/antiox6020025 · Cited by 250 · see citing works
The intracellular redox state is a core determinant of mitochondrial fusion
Shutt, T. E., Geoffrion, M., Milne, R. W., & McBride, H. M. (2012) · EMBO Reports · doi:10.1038/embor.2012.128 · Cited by 243 · see citing works
Structure, function, and regulation of mitofusin‐2 in health and disease
Chandhok, G., Lazarou, M., & Neumann, B. (2017) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12378 · Cited by 251 · see citing works
Pyakurel, A., Savoia, C., Hess, D., & Scorrano, L. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.021 · Cited by 244 · see citing works
Park, Y.-Y., Lee, S., Karbowski, M., Neutzner, A., Youle, R. J., & Cho, H. (2010) · Journal of Cell Science · doi:10.1242/jcs.061481 · Cited by 244 · see citing works
The Soluble Form of Bax Regulates Mitochondrial Fusion via MFN2 Homotypic Complexes
Hoppins, S. C., Edlich, F., Harwig, M. C., Banerjee, S., McCaffery, J. M., Youle, R. J., & Nunnari, J. M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2010.11.030 · Cited by 243 · see citing works
Mitochondrial dynamics in the adult cardiomyocytes: which roles for a highly specialized cell?
Piquereau, J., Caffin, F., Novotová, M., Lemaire, C., Veksler, V., Garnier, A., Ventura‐Clapier, R., & Joubert, F. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00102 · Cited by 235 · see citing works
Filadi, R., Theurey, P., & Pizzo, P. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.01.003 · Cited by 237 · see citing works
Inhibiting the Mitochondrial Fission Machinery Does Not Prevent Bax/Bak-Dependent Apoptosis
Parone, P. A., James, D. I., Cruz, S. D., Mattenberger, Y., Donzé, O., Barja, F., & Martinou, J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02282-05 · Cited by 231 · see citing works
Mitochondrial diseases: from molecular mechanisms to therapeutic advances
Wen, H., Deng, H., Li, B., Chen, J., Zhu, J., Zhang, X., Yoshida, S., & Zhou, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02044-3 · Cited by 248 · see citing works
Mitochondrial dynamics and their potential as a therapeutic target
Whitley, B. N., Engelhart, E. A., & Hoppins, S. C. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.06.002 · Cited by 223 · see citing works
Mitofusins 1 and 2 Are Essential for Postnatal Metabolic Remodeling in Heart
Papanicolaou, K. N., Kikuchi, R., Ngoh, G. A., Coughlan, K. A., Dominguez, I. M., Stanley, W. C., & Walsh, K. X. (2012) · Circulation Research · doi:10.1161/circresaha.112.274142 · Cited by 217 · see citing works
Therapeutic potential of targeting mitochondrial dynamics in cancer
Rodrigues, T., & Ferraz, L. S. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114282 · Cited by 218 · see citing works
MFN2 mutations cause severe phenotypes in most patients with CMT2A
Feely, S. M. E., Laurá, M., Siskind, C. E., Sottile, S. L., Davis, M. B., Gibbons, V. S., Reilly, M. M., & Shy, M. E. (2011) · Neurology · doi:10.1212/wnl.0b013e31821a441e · Cited by 217 · see citing works
Yue, W., Chen, Z., Liu, H., Chen, Y., Chen, M., Feng, D., Yan, C., Wu, H., Du, L., Wang, Y., et al. (2014) · Cell Research · doi:10.1038/cr.2014.20 · Cited by 213 · see citing works
Simmen, T., Lynes, E. M., Gesson, K., & Thomas, G. (2010) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.04.009 · Cited by 211 · see citing works
Mitochondrial Dynamics in Cardiovascular Health and Disease
Ong, S., Hall, A. R., & Hausenloy, D. J. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4777 · Cited by 204 · see citing works
Mitochondrial Dynamics in Stem Cells and Differentiation
Seo, B. J., Yoon, S. H., & Tae, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123893 · Cited by 201 · see citing works
Mitochondrial dynamics and transport in Alzheimer's disease
Flannery, P. J., & Trushina, E. V. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.06.009 · Cited by 198 · see citing works
Papanicolaou, K. N., Ngoh, G. A., Dabkowski, E. R., O’Connell, K. A., Júnior, R. F. R., Stanley, W. C., & Walsh, K. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00833.2011 · Cited by 202 · see citing works
Bhatia, D., Capili, A. M., & Choi, M. E. (2020) · Kidney Research and Clinical Practice · doi:10.23876/j.krcp.20.082 · Cited by 205 · see citing works
Romanello, V., & Sandri, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03662-0 · Cited by 197 · see citing works
Mitochondrial fusion proteins: Dual regulators of morphology and metabolism
Zorzano, A., Liesa, M., Sebastián, D., Segalés, J., & Palacı́n, M. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.01.002 · Cited by 193 · see citing works
Diet impact on mitochondrial bioenergetics and dynamics
Putti, R., Sica, R., Migliaccio, V., & Lionetti, L. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00109 · Cited by 192 · see citing works
Tur, J., Pereira‐Lopes, S., Vico, T., Marín, E., Muñoz, J. P., Hernández‐Álvarez, M. I., Cardona, P.-J., Antonio Zorzano, A., Lloberas, J., & Celada, A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108079 · Cited by 192 · see citing works
- Authors
- Ishihara, N., Eura, Y., & Mihara, K.
- Affiliations
- Kyushu University (JP)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2004-12-15
- Volume
- 117
- Issue
- 26
- Pages
- 6535-6546
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2171775338
- Cited by
- 731
- References
- 31
- Citations by year
- 2026: 17 · 2025: 35 · 2024: 38 · 2023: 44 · 2022: 39 · 2021: 65 · 2020: 54 · 2019: 47 · 2018: 46 · 2017: 38 · 2016: 34 · 2015: 18 · 2014: 24 · 2013: 30 · 2012: 34
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitofusin 1, mitofusin 2, mitochondrial fusion, GTPase activity, mitochondrial morphology, protein oligomerization, cis complexes
- MeSH terms
- Centrifugation, Density Gradient, Electrophoresis, Polyacrylamide Gel, HeLa Cells, Humans, Membrane Fusion, Membrane Proteins, Mitochondria, Precipitin Tests, Recombinant Fusion Proteins, Microscopy, Confocal, GTP Phosphohydrolases, Mitochondrial Proteins, Membrane Transport Proteins, Mitochondrial Membrane Transport Proteins, Green Fluorescent Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
