The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission
Open accessAbstract
Mitochondrial morphology is controlled by two opposing processes: fusion and fission. Drp1 (dynamin-related protein 1) and hFis1 are two key players of mitochondrial fission, but how Drp1 is recruited to mitochondria and how Drp1-mediated mitochondrial fission is regulated in mammals is poorly understood. Here, we identify the vertebrate-specific protein MIEF1 (mitochondrial elongation factor 1; independently identified as MiD51), which is anchored to the outer mitochondrial membrane. Elevated MIEF1 levels induce extensive mitochondrial fusion, whereas depletion of MIEF1 causes mitochondrial fragmentation. MIEF1 interacts with and recruits Drp1 to mitochondria in a manner independent of hFis1, Mff (mitochondrial fission factor) and Mfn2 (mitofusin 2), but inhibits Drp1 activity, thus executing a negative effect on mitochondrial fission. MIEF1 also interacts with hFis1 and elevated hFis1 levels partially reverse the MIEF1-induced fusion phenotype. In addition to inhibiting Drp1, MIEF1 also actively promotes fusion, but in a manner distinct from mitofusins. In conclusion, our findings uncover a novel mechanism which controls the mitochondrial fusion-fission machinery in vertebrates. As MIEF1 is vertebrate-specific, these data also reveal important differences between yeast and vertebrates in the regulation of mitochondrial dynamics.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“MIEF1/MiD51 and the variant MIEF2/MiD49 recruit DRP1 to mitochondria independent of MFF, but in contrast to MFF, inhibit DRP1 GTPase activity leading to mitochondrial elongation when MiD49/51 is overexpressed [92, 95, 96].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [95]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Site-directed mutagenesis by overlap extension using the polymerase chain reaction
Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K., & Pease, L. R. (1989) · Gene · doi:10.1016/0378-1119(89)90358-2 · Cited by 7,414
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
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
Delettre, C., Lenaers, G., Griffoin, J.-M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., et al. (2000) · Nature Genetics · doi:10.1038/79936 · Cited by 1,446
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
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
Otera, H., Wang, C., Cleland, M. M., Setoguchi, K., Yokota, S., Youle, R. J., & Mihara, K. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201007152 · Cited by 1,110
Mitochondria in neuroplasticity and neurological disorders
Mattson, M. P., Gleichmann, M., & Cheng, A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.010 · Cited by 1,081
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
Cribbs, J. T., & Strack, S. (2007) · EMBO Reports · doi:10.1038/sj.embor.7401062 · Cited by 1,061
Roles 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
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
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
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
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
Chang, C., & Blackstone, C. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700083200 · Cited by 824
Yoon, Y., Krueger, E. W., Oswald, B. J., & McNiven, M. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5409-5420.2003 · Cited by 820
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
Gandre-Babbe, S., & van der Bliek, A. M. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-12-1287 · Cited by 769
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
A Human Dynamin-related Protein Controls the Distribution of Mitochondria
Смирнова, Е. А., Shurland, D., Ryazantsev, S. N., & van der Bliek, A. M. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.2.351 · Cited by 734
Mozdy, A. D., McCaffery, J. M., & Shaw, J. M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.367 · Cited by 731
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
hFis1, a Novel Component of the Mammalian Mitochondrial Fission Machinery
James, D. I., Parone, P. A., Mattenberger, Y., & Martinou, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303758200 · Cited by 653
MiD49 and MiD51, new components of the mitochondrial fission machinery
Palmer, C. S., Osellame, L. D., Laine, D., Koutsopoulos, O. S., Frazier, A. E., & Ryan, M. T. (2011) · The EMBO Reports · doi:10.1038/embor.2011.54 · Cited by 649
Inhibition of mitochondrial fusion by α‐synuclein is rescued by PINK1, Parkin and DJ‐1
Kamp, F., Exner, N., Lutz, A. K., Wender, N., Hegermann, J., Brunner, B., Nuscher, B., Bartels, T., Giese, A., Beyer, K., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.223 · Cited by 504
Eura, Y. (2003) · Journal of Biochemistry · doi:10.1093/jb/mvg150 · Cited by 445
CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology
Han, X.-J., Lü, Y.-F., Li, S.-A., Kaitsuka, T., Sato, Y., Tomizawa, K., Nairn, A. C., Takei, K., Matsui, H., & Matsushita, M. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200802164 · Cited by 435
Tieu, Q., & Nunnari, J. M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.353 · Cited by 375
Systematic subcellular localization of novel proteins identified by large‐scale cDNA sequencing
Simpson, J. C., Wellenreuther, R., Poustka, A., Pepperkok, R., & Wiemann, S. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd058 · Cited by 354
Mitochondrial dysfunction in cancer
Modica-Napolitano, J. S., & Singh, K. K. (2004) · Mitochondrion · doi:10.1016/j.mito.2004.07.027 · Cited by 299
Mammalian Dynamin-like Protein DLP1 Tubulates Membranes
Yoon, Y., Pitts, K. R., & McNiven, M. A. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.9.2894 · Cited by 285
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 284
Self-citationGriffin, E. E., Graumann, J., & Chan, D. C. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200503148 · Cited by 265
Zhu, P.-P., Patterson, A. D., Stadler, J., Seeburg, D. P., Sheng, M., & Blackstone, C. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404105200 · Cited by 221
Tieu, Q., Okreglak, V., Naylor, K., & Nunnari, J. M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200205031 · Cited by 217
Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes
Zorzano, A., Liesa, M., & Palacín, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.02.004 · Cited by 209
Morphological dynamics of mitochondria — A special emphasis on cardiac muscle cells
Hom, J., & Sheu, S. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.02.023 · Cited by 189
Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1β
Liesa, M., Borda-d'Agua, B., Medina‐Gómez, G., Lelliott, C. J., Paz, J. C., Rojo, M., Palacín, M., Vidal‐Puig, A., & Antonio Zorzano, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003613 · Cited by 182
Mitochondrial dynamics and cancer
Grandemange, S., Herzig, S., & Martinou, J. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.12.001 · Cited by 180
Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1
Yu, T., Fox, R. J., Burwell, L. S., & Yoon, Y. (2005) · Journal of Cell Science · doi:10.1242/jcs.02537 · Cited by 171
Mitochondrial structural and functional dynamics in Huntington's disease
Reddy, P. H., Mao, P., & Mańczak, M. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.04.001 · Cited by 164
Suzuki, M., Jeong, S.-Y., Karbowski, M., Youle, R. J., & Tjandra, N. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.09.064 · Cited by 161
Santel, A., & Frank, S. (2008) · IUBMB Life · doi:10.1002/iub.71 · Cited by 152
Mitochondrial fission and fusion dynamics: the long and short of it
Berman, S., Pineda, F. J., & Hardwick, J. M. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.57 · Cited by 147
Huang, P., Yu, T., & Yoon, Y. (2007) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2007.04.002 · Cited by 131
Palma, C. D., Falcone, S., Pisoni, S., Cipolat, S., Panzeri, M. C., Pambianco, S., Pisconti, A., Allevi, R., Bassi, M. T., Cossu, G., et al. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.48 · Cited by 119
Identification of a Novel Mitochondrial Complex Containing Mitofusin 2 and Stomatin-like Protein 2
Hájek, P., Chomyn, A., & Attardi, G. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608168200 · Cited by 111
Westermann, B. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.12.003 · Cited by 105
Lackner, L. L., & Nunnari, J. M. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.05.016 · Cited by 101
Molecular machinery of mitochondrial dynamics in yeast
Merz, S., Hammermeister, M., Altmann, K., Dürr, M., & Westermann, B. (2007) · Biological Chemistry · doi:10.1515/bc.2007.110 · Cited by 50
Zhao, J., Liu, T., Jin, S., Tomilin, N. V., Castro, J., Shupliakov, O., Lendahl, U., & Nistér, M. (2009) · Journal of Cell Science · doi:10.1242/jcs.038513 · Cited by 46
Self-citationCell Biology of Mitochondrial Dynamics
Kiefel, B. R., Gilson, P. R., & Beech, P. L. (2006) · International review of cytology · doi:10.1016/s0074-7696(06)54004-5 · Cited by 44
Emerging roles of mitochondrial membrane dynamics in health and disease
Schäfer, A., & Reichert, A. S. (2009) · Biological Chemistry · doi:10.1515/bc.2009.086 · Cited by 32
Flagged first, then by citations
Cited by
Sorted by citations
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
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
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
Mitochondrial Dynamics — Mitochondrial Fission and Fusion in Human Diseases
Archer, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1215233 · Cited by 1,120
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 903
Metadata
- Authors
- Zhao, J., Liu, T., Jin, S., Wang, X., Qu, M., Uhlén, P., Tomilin, N., Shupliakov, O., Lendahl, U., & Nistér, M.
- Affiliations
- Karolinska University Hospital (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Zhao, Jian
- Lendahl, Urban
- Nistér, Monica
- Venue
- The EMBO Journal
- Published
- 2011-06-24
- Volume
- 30
- Issue
- 14
- Pages
- 2762-2778
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3160255
- OpenAlex
- W1960363048
- Cited by
- 370
- References
- 54
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 14 · 2023: 22 · 2022: 17 · 2021: 30 · 2020: 25 · 2019: 19 · 2018: 27 · 2017: 27 · 2016: 27 · 2015: 33 · 2014: 38 · 2013: 37 · 2012: 26
- FWCI
- 14.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- University of Rochester
- Cancerfonden
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Deutsches Zentrum für Neurodegenerative Erkrankungen
- Barncancerfonden
- Cancerföreningen i Stockholm
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- MiD51, Drp1, mitochondrial fusion, mitochondrial fission, mitochondrial dynamics, mitochondrial outer membrane, mitochondrial fragmentation, mitofusins
- MeSH terms
- Cross-Linking Reagents, Cytoplasm, Fluorescent Antibody Technique, Glioma, HeLa Cells, Humans, Immunoenzyme Techniques, Membrane Fusion, Membrane Proteins, Microtubule-Associated Proteins, Mitochondria, Neuroblastoma, Peptide Elongation Factors, Protein Binding, RNA, Messenger, Subcellular Fractions, Tumor Cells, Cultured, Blotting, Western, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, RNA, Small Interfering, Immunoprecipitation, Mitochondrial Membranes
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
