Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development
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Mitochondrial morphology is determined by a dynamic equilibrium between organelle fusion and fission, but the significance of these processes in vertebrates is unknown. The mitofusins, Mfn1 and Mfn2, have been shown to affect mitochondrial morphology when overexpressed. We find that mice deficient in either Mfn1 or Mfn2 die in midgestation. However, whereas Mfn2 mutant embryos have a specific and severe disruption of the placental trophoblast giant cell layer, Mfn1-deficient giant cells are normal. Embryonic fibroblasts lacking Mfn1 or Mfn2 display distinct types of fragmented mitochondria, a phenotype we determine to be due to a severe reduction in mitochondrial fusion. Moreover, we find that Mfn1 and Mfn2 form homotypic and heterotypic complexes and show, by rescue of mutant cells, that the homotypic complexes are functional for fusion. We conclude that Mfn1 and Mfn2 have both redundant and distinct functions and act in three separate molecular complexes to promote mitochondrial fusion. Strikingly, a subset of mitochondria in mutant cells lose membrane potential. Therefore, mitochondrial fusion is essential for embryonic development, and by enabling cooperation between mitochondria, has protective effects on the mitochondrial population.
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Genetic loss of MFN1 induces a higher degree of mitochondrial fragmentation than MFN2 deletion.
“Genetic loss of MFN1 induces a higher degree of mitochondrial fragmentation than MFN2 deletion [60].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [60]
Mitochondrial fusion rates correlate with OXPHOS capacity, being higher in oxidative fibers than in glycolytic fibers.
“Mitochondrial fusion rates correlate with the OXPHOS capacity, higher in oxidative fibers than in glycolytic fibers [60].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [60]
Full knockout mice of either Mfn1, Mfn2, or OPA1 result in embryonic lethality, demonstrating the biological importance of mitochondrial fusion in early development.
“The full knockout mice of either Mfn1, Mfn2, or OPA1 result in embryonic lethality of mice, demonstrating the biological importance of mitochondrial fusion in early development [60, 178].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [60]
Both Mfn proteins mediate fusion through their active GTPase domains by tethering opposing mitochondrial membranes.
“Both Mfn proteins mediate fusion through their active GTPase domains by tethering opposing mitochondrial membranes (Chen et al., 2003; Eura et al., 2003).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Chen et al., 2003
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Cites
The GTPase superfamily: conserved structure and molecular mechanism
Bourne, H. R., Sanders, D. A., & McCormick, F. (1991) · Nature · doi:10.1038/349117a0 · Cited by 3,392 · see citing works
Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., & Pozzan, T. (1998) · Science · doi:10.1126/science.280.5370.1763 · Cited by 2,257 · see citing works
Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein
Vortkamp, A., Lee, K., Lanske, B., Segre, G. V., Kronenberg, H. M., & Tabin, C. J. (1996) · Science · doi:10.1126/science.273.5275.613 · Cited by 1,999 · see citing works
Dynamin-related Protein Drp1 Is Required for Mitochondrial Division in Mammalian Cells
Smirnova, E., Griparić, L., Shurland, D., & van der Bliek, A. M. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.8.2245 · Cited by 1,938 · 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
Promotion of Trophoblast Stem Cell Proliferation by FGF4
Tanaka, S., Kunath, T., Hadjantonakis, A., Nagy, A., & Rossant, J. (1998) · Science · doi:10.1126/science.282.5396.2072 · Cited by 1,370 · see citing works
Coiled coils: new structures and new functions.
Lupas, A. (1996) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/s0968-0004(96)10052-9 · Cited by 1,191 · see citing works
G PROTEIN MECHANISMS: Insights from Structural Analysis
Sprang, S. R. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.639 · Cited by 1,057 · 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
Bereiter‐Hahn, J., & Vöth, M. (1994) · Microscopy Research and Technique · doi:10.1002/jemt.1070270303 · Cited by 900 · see citing works
Edgar, B. A., & Orr‐Weaver, T. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00334-8 · Cited by 843 · see citing works
Coiled coils: new structures and new functions
Lupas, A. N. (1996) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(96)10052-9 · Cited by 836 · 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
Mozdy, A. D., McCaffery, J. M., & Shaw, J. M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.367 · Cited by 725 · see citing works
Tanaka, Y., Kanai, Y., Okada, Y., Nonaka, S., Takeda, S., Harada, A., & Hirokawa, N. (1998) · Cell · doi:10.1016/s0092-8674(00)81459-2 · Cited by 654 · see citing works
[6] Efficient site-directed mutagenesis using uracil-containing DNA
Kunkel, T. A., Bębenek, K., & McClary, J. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)04008-c · Cited by 642 · 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
KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria
Nangaku, M., Sato-Yoshitake, R., Okada, Y., Noda, Y., Takemura, R., Yamazaki, H., & Hirokawa, N. (1994) · Cell · doi:10.1016/0092-8674(94)90012-4 · Cited by 598 · see citing works
Mitochondria are morphologically and functionally heterogeneous within cells
Collins, T. J., Berridge, M. J., Lipp, P., & Bootman, M. D. (2002) · The EMBO Journal · doi:10.1093/emboj/21.7.1616 · Cited by 588 · 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
Axonal transport of mitochondria along microtubules and F-actin in living vertebrate neurons.
Morris, R. L., & Hollenbeck, P. J. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.131.5.1315 · Cited by 541 · see citing works
The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis
Riley, P. R., Anaon-Cartwight, L., & Cross, J. C. (1998) · Nature Genetics · doi:10.1038/ng0398-271 · Cited by 536 · 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
Nakada, K., Inoue, K., Ono, T., Isobe, K., Ogura, A., Goto, Y., Nonaka, I., & Hayashi, J. (2001) · Nature Medicine · doi:10.1038/90976 · Cited by 430 · see citing works
Ono, T., Isobe, K., Nakada, K., & Hayashi, J.-I. (2001) · Nature Genetics · doi:10.1038/90116 · Cited by 420 · see citing works
Tieu, Q., & Nunnari, J. M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.353 · 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
Death before birth: clues from gene knockouts and mutations
Copp, A. J. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89008-3 · Cited by 368 · see citing works
Genetic insights into trophoblast differentiation and placental morphogenesis
Cross, J. C. (2000) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.2000.0156 · Cited by 263 · see citing works
Scott, I. C., Anson‐Cartwright, L., Riley, P. R., Reda, D., & Cross, J. C. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.2.530-541.2000 · Cited by 229 · see citing works
Mitochondrial framework (reticulum mitochondriale) in rat diaphragm muscle
Bakeeva, L. E., Chentsov, Y. S., & Skulachev, V. P. (1978) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(78)90104-4 · Cited by 227 · see citing works
Chester, N., Kuo, F. C., Kozak, C. A., O’Hara, C., & Leder, P. (1998) · Genes & Development · doi:10.1101/gad.12.21.3382 · Cited by 203 · see citing works
Isolation and characterization of a novel trophoblast-specific cDNA in the mouse.Preprint
Lescisin, K. R., Varmuza, S., & Rossant, J. (1988) · Genes & Development · doi:10.1101/gad.2.12a.1639 · Cited by 191 · see citing works
Gag3p, an Outer Membrane Protein Required for Fission of Mitochondrial Tubules
Fekkes, P., Shepard, K. A., & Yaffe, M. P. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.333 · Cited by 178 · see citing works
Jat, P., Cepko, C. L., Mulligan, R. C., & Sharp, P. A. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.4.1204 · Cited by 176 · see citing works
Targeted deletion of keratins 18 and 19 leads to trophoblast fragility and early embryonic lethality
Hesse, M., Franz, T., Tamai, Y., Taketo, M. M., & Magin, T. M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.19.5060 · Cited by 169 · see citing works
Trophoblastic Giant Cells of the Mouse Placenta as the Site of Proliferin Synthesis*
Lee, S. M., Talamantes, F. J., WILDER, E., Linzer, D. I. H., & Nathans, D. (1988) · Endocrinology · doi:10.1210/endo-122-5-1761 · Cited by 143 · see citing works
Human mitochondria and mitochondrial genome function as a single dynamic cellular unit.
Hayashi, J.-I., Takemitsu, M., Goto, Y., & Nonaka, I. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.125.1.43 · Cited by 142 · see citing works
Okada, A., Lansford, R. D., Weimann, J. M., Fraser, S. E., & McConnell, S. K. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7033 · Cited by 124 · see citing works
Self-citationRequirement of the mouse I‐mfa gene for placental development and skeletal patterning
Kraut, N., Snider, L. D., Chen, C.-M. A., Tapscott, S. J., & Groudine, M. T. (1998) · The EMBO Journal · doi:10.1093/emboj/17.21.6276 · Cited by 111 · see citing works
Localization of Placental Lactogen-l in Trophoblast Giant Cells of the Mouse Placenta1
Faria, T. N., Ogren, L., Talamantes, F. J., Linzer, D. I. H., & Soares, M. J. (1991) · Biology of Reproduction · doi:10.1095/biolreprod44.2.327 · Cited by 109 · see citing works
Enrı́quez, J. A., Cabezas‐Herrera, J., Bayona‐Bafaluy, M. P., & Attardi, G. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.15.11207 · Cited by 94 · see citing works
Differential expression of the Drosophila mitofusin genes fuzzy onions (fzo) and dmfn
Hwa, J. J., Hiller, M. A., Fuller, M. T., & Santel, A. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(02)00141-7 · Cited by 89 · see citing works
Intermitochondrial contacts in myocardiocytes
Bakeeva, L. E. (1983) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(83)90261-4 · Cited by 76 · see citing works
Jat, P., Cepko, C. L., Mulligan, R. C., et al. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.4.1204-1217.1986 · Cited by 72 · see citing works
Ontogenesis of mitochondrial reticulum in rat diaphragm muscle.
Bakeeva, L. E., Chentsov, Y. S., & Skulachev, V. P. (1981) · PubMed · Cited by 56 · see citing works
Pre-eclampsia: a disorder of placental mitochondria?
Widschwendter, M., Schröcksnadel, H., & Mörtl, M. (1998) · Molecular Medicine Today · doi:10.1016/s1357-4310(98)01293-3 · Cited by 52 · see citing works
Interaction Theory of Mammalian Mitochondria
Nakada, K., Inoue, K., & Hayashi, J. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5838 · Cited by 47 · see citing works
Molecular and Genetic Aspects of Preeclampsia: State of the Art
Tálosi, G., Endreffy, E., Túri, S., & Németh, I. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3099 · Cited by 20 · see citing works
Potentiometric Membrane Dyes and Imaging Membrane Potential in Single Cells
Loew, L. M. (1999) · Elsevier eBooks · doi:10.1016/b978-012447836-7/50016-6 · Cited by 11 · see citing works
Hoang, B. H., Thomas, J. T., Abdul-Karim, F. W., Correia, K. M., Conlon, R. A., Luyten, F. P., & Ballock, R. T. (1998) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199807)212:3
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Mitochondria: In Sickness and in Health
Nunnari, J., & Suomalainen, A. (2012) · Cell · doi:10.1016/j.cell.2012.02.035 · Cited by 3,479 · see citing works
Calcium, ATP, and ROS: a mitochondrial love-hate triangle
Brookes, P. S., Yoon, Y., Robotham, J. L., Anders, M. W., & Sheu, S.-S. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00139.2004 · Cited by 2,575 · see citing works
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
Mitochondrial fusion and fission in cell life and death
Westermann, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3013 · Cited by 2,002 · see citing works
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
Chan, D. C. (2006) · Cell · doi:10.1016/j.cell.2006.06.010 · Cited by 1,987 · see citing works
Self-citationMitochondria: 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
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
Mitochondrial Dynamics and Its Involvement in Disease
Chan, D. C. (2020) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012419-032711 · Cited by 1,416 · see citing works
Self-citationMitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases
Chen, H., & Chan, D. C. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp326 · Cited by 1,455 · see citing works
Self-citationMitochondrial Dynamics Controls T Cell Fate through Metabolic Programming
Buck, M. D., O’Sullivan, D., Geltink, R. I. K., Curtis, J. D., Chang, C., Sanin, D. E., Qiu, J., Kretz, O., Braas, D., van der Windt, G. J. W., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.035 · Cited by 1,444 · 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
Self-citationFunctions and dysfunctions of mitochondrial dynamics
Detmer, S. A., & Chan, D. C. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2275 · Cited by 1,369 · see citing works
Self-citationMitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial Dynamics
Martinou, J., & Youle, R. J. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.017 · Cited by 1,366 · see citing works
OPA1 requires mitofusin 1 to promote mitochondrial fusion
Cipolat, S., de Brito, O. M., Dal Zilio, B., & Scorrano, L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407043101 · Cited by 1,300 · see citing works
Mitochondrial Dynamics and Metabolic Regulation
Wai, T., & Langer, T. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.12.001 · Cited by 1,304 · see citing works
Cogliati, S., Frezza, C., Soriano, M. E., Varanita, T., Quintana-Cabrera, R., Corrado, M., Cipolat, S., Costa, V., Casarin, A., Gomes, L. C., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.032 · Cited by 1,265 · see citing works
Mitochondrial dynamics in health and disease: mechanisms and potential targets
Chen, W., Zhao, H., & Li, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01547-9 · Cited by 1,306 · 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
Mitochondrial Oxidative Stress: Implications for Cell Death
Orrenius, S., Gogvadze, V. G., & Zhivotovsky, B. (2006) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105122 · Cited by 1,266 · see citing works
Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission
Losón, O. C., Song, Z., Chen, H., & Chan, D. C. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-10-0721 · Cited by 1,235 · see citing works
Self-citationChen, H., Vermulst, M., Wang, Y. E., Chomyn, A., Prolla, T. A., McCaffery, J. M., & Chan, D. C. (2010) · Cell · doi:10.1016/j.cell.2010.02.026 · Cited by 1,211 · see citing works
Self-citationMitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission.
Taguchi, N., Ishihara, N., Jofuku, A., Oka, T., & Mihara, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607279200 · Cited by 1,226 · see citing works
Fusion and fission: interlinked processes critical for mitochondrial health
Chan, D. C. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110410-132529 · Cited by 1,196 · see citing works
Self-citationRambold, 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
Metabolic regulation of mitochondrial dynamics
Mishra, P., & Chan, D. C. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201511036 · Cited by 1,096 · see citing works
Self-citationMitochondrial Dynamics — Mitochondrial Fission and Fusion in Human Diseases
Archer, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1215233 · Cited by 1,103 · see citing works
Ishihara, N., Nomura, M., Jofuku, A., Kato, H., Suzuki, S. O., Masuda, K., Otera, H., Nakanishi, Y., Nonaka, I., Goto, Y.-I., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1907 · Cited by 1,066 · see citing works
Mitochondrial dynamics and inheritance during cell division, development and disease
Mishra, P., & Chan, D. C. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3877 · Cited by 1,038 · see citing works
Self-citationRoles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis
Lee, Y.-J., Jeong, S.-Y., Karbowski, M., Smith, C. L., & Youle, R. J. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-04-0294 · Cited by 1,042 · see citing works
Endoplasmic reticulum-mitochondria contacts: Function of the junction
Rowland, A. A., & Voeltz, G. K. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3440 · Cited by 1,018 · 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
Broad activation of the ubiquitin–proteasome system by Parkin is critical for mitophagy
Chan, N. C., Salazar, A. M., Pham, A. H., Sweredoski, M. J., Kolawa, N. J., Graham, R. L. J., Hess, S., & Chan, D. C. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr048 · Cited by 993 · see citing works
Self-citationMitochondrial 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
Self-citationMitochondrial 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
Mitochondrial fusion protects against neurodegeneration in the cerebellum
Chen, H., McCaffery, J. M., & Chan, D. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.026 · Cited by 924 · see citing works
Self-citationStructural 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
Self-citationMitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration
Sheng, Z., & Cai, Q. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3156 · Cited by 906 · see citing works
Cellular and molecular mechanisms of mitochondrial function
Osellame, L. D., Blacker, T. S., & Duchen, M. R. (2012) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2012.05.003 · Cited by 871 · see citing works
Mechanisms of Mitochondrial Fission and FusionPreprint
van der Bliek, A. M., Shen, Q., & Kawajiri, S. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a011072 · Cited by 861 · see citing works
Wang, X., Su, B., Siedlak, S. L., Moreira, P. I., Fujioka, H., Wang, Y., Casadesus, G., & Zhu, X. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804871105 · Cited by 835 · see citing works
Song, Z., Chen, H., Fiket, M., Alexander, C., & Chan, D. C. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200704110 · Cited by 818 · 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
Kubli, D. A., & Gustafsson, Å. B. (2012) · Circulation Research · doi:10.1161/circresaha.112.265819 · Cited by 792 · 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
Gandre-Babbe, S., & van der Bliek, A. M. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-12-1287 · Cited by 769 · see citing works
SLP‐2 is required for stress‐induced mitochondrial hyperfusion
Tondera, D., Grandemange, S., Jourdain, A. A., Karbowski, M., Mattenberger, Y., Herzig, S., Cruz, S. D., Clerc, P., Lauria, I., Merkwirth, C., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.89 · Cited by 767 · see citing works
Self-citationAxonal transport deficits and neurodegenerative diseases
Millecamps, S., & Julien, J.-P. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3380 · Cited by 755 · 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
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
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
Role of Axonal Transport in Neurodegenerative Diseases
Vos, K. J. D., Grierson, A. J., Ackerley, S., & Miller, C. C. J. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.061307.090711 · Cited by 734 · see citing works
Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity
Ishihara, N., Eura, Y., & Mihara, K. (2004) · Journal of Cell Science · doi:10.1242/jcs.01565 · Cited by 731 · 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
The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice
Wakabayashi, J., Zhang, Z., Wakabayashi, N., Tamura, Y., Fukaya, M., Kensler, T. W., Iijima, M., & Sesaki, H. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200903065 · Cited by 667 · see citing works
Bioenergetic role of mitochondrial fusion and fission
Westermann, B. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.02.033 · Cited by 687 · see citing works
Khacho, M., Clark, A., Svoboda, D. S., Azzi, J., MacLaurin, J. G., Meghaizel, C., Sesaki, H., Lagace, D. C., Germain, M., Harper, M., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.04.015 · Cited by 672 · see citing works
Here, there, and everywhere: The importance of ER membrane contact sites
Wu, H., Carvalho, P., & Voeltz, G. K. (2018) · Science · doi:10.1126/science.aan5835 · Cited by 688 · see citing works
Sebastián, D., Hernández-Alvarez, M. I., Segalés, J., Sorianello, E., Muñoz, J. P., Sala, D., Waget, A., Liesa, M., Paz, J. C., Gopalacharyulu, P., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108220109 · Cited by 673 · see citing works
MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond
Vance, J. E. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.11.014 · Cited by 665 · see citing works
Disturbed mitochondrial dynamics and neurodegenerative disorders
Burté, F., Carelli, V., Chinnery, P. F., & Yu‐Wai‐Man, P. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.228 · Cited by 659 · see citing works
Nitric oxide‐induced mitochondrial fission is regulated by dynamin‐related GTPases in neurons
Barsoum, M. J., Yuan, H., Gerencser, A. A., Liot, G., Kushnareva, Y., Gräber, S., Kovács, I., Lee, W. D., Waggoner, J., Cui, J., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601253 · Cited by 658 · 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
Mitra, K., Wunder, C., Roysam, B., Lin, G., & Lippincott‐Schwartz, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904875106 · Cited by 625 · 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
Mitochondrial dynamics in adaptive and maladaptive cellular stress responses
Eisner, V., Picard, M., & Hajnóczky, G. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0133-0 · Cited by 622 · see citing works
Benador, I. Y., Veliova, M., Mahdaviani, K., Petcherski, A., Wikström, J. D., Assali, E. A., Acín‐Pérez, R., Shum, M., de Oliveira, M. F., Cinti, S., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.003 · Cited by 621 · see citing works
Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion
Song, Z., Ghochani, M., McCaffery, J. M., Frey, T. G., & Chan, D. C. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-03-0252 · Cited by 623 · see citing works
Self-citationCalcium Signaling and Reactive Oxygen Species in Mitochondria
Bertero, E., & Maack, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.310082 · Cited by 616 · see citing works
The GTPase dMiro Is Required for Axonal Transport of Mitochondria to Drosophila Synapses
Guo, X., Macleod, G. T., Wellington, A. J., Hu, F., Panchumarthi, S., Schoenfield, M., Marin, L., Charlton, M. P., Atwood, H. L., & Zinsmaier, K. E. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.027 · Cited by 619 · see citing works
FOXO transcription factors: key regulators of cellular quality control
Webb, A. E., & Brunet, A. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.003 · Cited by 620 · see citing works
Nakamura, K., Nemani, V., Azarbal, F., Skibinski, G., Levy, J. M., Egami, K., Munishkina, L. A., Zhang, J., Gardner, B. M., Wakabayashi, J., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.213538 · Cited by 590 · see citing works
Triclosan exposure, transformation, and human health effects
Weatherly, L. M., & Gosse, J. A. (2017) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2017.1399306 · Cited by 591 · see citing works
Tezze, C., Romanello, V., Desbats, M. A., Fadini, G. P., Albiero, M., Favaro, G., Ciciliot, S., Soriano, M. E., Morbidoni, V., Cerqua, C., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.021 · Cited by 568 · see citing works
“Mouse knockouts (KO) for each of the pro-fusion genes ( Mfn1 , Mfn2 , and Opa1 ) are lethal to embryos because of mitochondrial dysfunction (Chen et al., 2003; Davies et al., 2007).”
Maltepe, E., & Fisher, S. J. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100814-125620 · Cited by 592 · see citing works
Song, W., Chen, J., Petrilli, A. M., Liot, G., Klinglmayr, E., Zhou, Y., Poquiz, P., Tjong, J., Pouladi, M. A., Hayden, M. R., et al. (2011) · Nature Medicine · doi:10.1038/nm.2313 · Cited by 556 · see citing works
A Class of Dynamin-like GTPases Involved in the Generation of the Tubular ER Network
Hu, J., Shibata, Y., Zhu, P., Voss, C., Rismanchi, N., Prinz, W. A., Rapoport, T. A., & Blackstone, C. D. (2009) · Cell · doi:10.1016/j.cell.2009.05.025 · Cited by 540 · see citing works
Emerging functions of mammalian mitochondrial fusion and fission
Chen, H., & Chan, D. C. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi270 · Cited by 538 · see citing works
Self-citationPhosphatidylethanolamine Metabolism in Health and Disease
Calzada, E., Onguka, O., & Claypool, S. M. (2015) · International review of cytology · doi:10.1016/bs.ircmb.2015.10.001 · Cited by 534 · see citing works
Mitochondrial-nuclear communications
Ryan, M. T., & Hoogenraad, N. J. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052305.091720 · Cited by 575 · 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
Quality control of mitochondria: protection against neurodegeneration and ageing
Tatsuta, T., & Langer, T. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601972 · Cited by 519 · see citing works
Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance
Schneeberger, M., Dietrich, M. O., Sebastián, D., Imbernón, M., Castaño, C., Garcia, A., Esteban, Y., Gonzalez-Franquesa, A., Rodríguez, I. C., Bortolozzi, A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.003 · Cited by 519 · see citing works
Energetics, epigenetics, mitochondrial genetics
Wallace, D. C., & Fan, W. (2009) · Mitochondrion · doi:10.1016/j.mito.2009.09.006 · Cited by 507 · 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
Song, M., Mihara, K., Chen, Y., Scorrano, L., & Dorn, G. W. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.011 · Cited by 482 · 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
MicroRNA Directly Enhances Mitochondrial Translation during Muscle Differentiation
Zhang, X., Zuo, X., Yang, B., Li, Z., Xue, Y., Zhou, Y., Huang, J. S., Zhao, X., Zhou, J., Yan, Y., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.047 · Cited by 488 · see citing works
New insights into the function and regulation of mitochondrial fission
Otera, H., Ishihara, N., & Mihara, K. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.02.002 · Cited by 476 · 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
Self-citationThe mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division
Karbowski, M., Neutzner, A., & Youle, R. J. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200611064 · Cited by 474 · see citing works
Varanita, T., Soriano, M. E., Romanello, V., Zaglia, T., Quintana-Cabrera, R., Semenzato, M., Menabò, R., Costa, V., Civiletto, G., Pesce, P., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.007 · Cited by 460 · see citing works
Mishra, P., Carelli, V., Manfredi, G., & Chan, D. C. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.011 · Cited by 473 · see citing works
Self-citationYu, T., Sheu, S.-S., Robotham, J. L., & Yoon, Y. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn104 · Cited by 462 · see citing works
Griparić, L., van der Wel, N. N., Orozco, I. J., Peters, P. J., & van der Bliek, A. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400920200 · Cited by 468 · see citing works
Mitochondrial dynamics in neurodegeneration
Itoh, K., Nakamura, K., Iijima, M., & Sesaki, H. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.10.006 · Cited by 464 · see citing works
- Authors
- Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C.
- Affiliations
- California Institute of Technology (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2003-01-13
- Volume
- 160
- Issue
- 2
- Pages
- 189-200
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2172648
- OpenAlex
- W2073095545
- Cited by
- 2,601
- References
- 52
- Citations by year
- 2026: 111 · 2025: 132 · 2024: 143 · 2023: 149 · 2022: 173 · 2021: 192 · 2020: 170 · 2019: 149 · 2018: 160 · 2017: 127 · 2016: 121 · 2015: 115 · 2014: 126 · 2013: 103 · 2012: 112
- FWCI
- 14.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Warwick Research Archive Portal (University of Warwick) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (1 R01 GM62967-01, R01GM062967, T32GM007616, GM07616)
- 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 › Cell death mechanisms and regulation
- Keywords
- mitofusins, Mfn1, mitofusin 2, mitochondrial fusion, mitochondrial fission, mitochondrial morphology, embryonic development, mitochondrial membrane potential, mitochondrial fragmentation, embryonic fibroblasts, mouse mutants
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Cytoskeletal Proteins, Embryo, Mammalian, Female, Embryonic and Fetal Development, Fetus, Genes, Lethal, Intracellular Membranes, Male, Membrane Potentials, Membrane Proteins, Mitochondria, Placenta, Trophoblasts, Mice, Knockout, Gene Expression Regulation, Developmental, GTP Phosphohydrolases, Embryo Loss, Mitochondrial Proteins, Membrane Transport Proteins, Mitochondrial Membrane Transport Proteins, Macromolecular Substances, Utrophin, Mice
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