The DOI matches its Crossref record; 45 of the 47 references it cites were found in a registry or an index.
Mitochondrial Fission and Fusion Factors Reciprocally Orchestrate Mitophagic Culling in Mouse Hearts and Cultured Fibroblasts
Open accessAbstract
How mitochondrial dynamism (fission and fusion) affects mitochondrial quality control is unclear. We uncovered distinct effects on mitophagy of inhibiting Drp1-mediated mitochondrial fission versus mitofusin-mediated mitochondrial fusion. Conditional cardiomyocyte-specific Drp1 ablation evoked mitochondrial enlargement, lethal dilated cardiomyopathy, and cardiomyocyte necrosis. Conditionally ablating cardiomyocyte mitofusins (Mfn) caused mitochondrial fragmentation with eccentric remodeling and no cardiomyocyte dropout. Parallel studies in cultured murine embryonic fibroblasts (MEFs) and in vivo mouse hearts revealed that Mfn1/Mfn2 deletion provoked accumulation of defective mitochondria exhibiting an unfolded protein response, without appropriately increasing mitophagy. Conversely, interrupting mitochondrial fission by Drp1 ablation increased mitophagy and caused a generalized loss of mitochondria. Mitochondrial permeability transition pore (MPTP) opening in Drp1 null mitochondria was associated with mitophagy in MEFs and contributed to cardiomyocyte necrosis and dilated cardiomyopathy in mice. Drp1, MPTP, and cardiomyocyte mitophagy are functionally integrated. Mitochondrial fission and fusion have opposing roles during in vivo cardiac mitochondrial quality control.
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“Moreover, Mfn2 has been shown to participate in mitophagy in cardiomyocytes (Chen & Dorn, 2013; Song et al, 2015).”
From Mfn2 deficiency links age‐related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway (2016) · cites this paper as Song et al, 2015
In the citing paper
“Impairment of fission leads to the disruption of selective mitochondrial autophagic degradation, followed by dysfunctional organelles accumulation [58, 196–200].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [200]
In the citing paper
“Disrupted mitochondrial fission, obtained with the specific ablation of DRP1 in the heart, induces accumulation of defective mitochondria due to impaired autophagy/mitophagy, that over-time promotes cardiomyocyte death [198–200].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [200]
In the citing paper
“Consistent with this crucial role, conditional ablation of DRP1 in the heart, brain, and skeletal muscle causes lethality [196, 198–200, 208, 209].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [200]
In the citing paper
“Energy stress consequent to acute or chronic exercise triggers autophagy in different tissues [197–200].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [200]
In the citing paper
“Mitophagy is intricately linked to mitochondrial dynamics [180,181,182].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [181]
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Cites
Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., SMEDT, H. D., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,131
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Narendra, D. P., Jin, S. M., Tanaka, A., Suen, D.-F., Gautier, C. A., Shen, J., Cookson, M. R., & Youle, R. J. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000298 · Cited by 2,944
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
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280
Self-citationGray, M. W., Burger, G., & Lang, B. F. (1999) · Science · doi:10.1126/science.283.5407.1476 · Cited by 1,765
PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria
Chen, Y., & Dorn, G. W. (2013) · Science · doi:10.1126/science.1231031 · Cited by 1,323
Self-citationKraupp, B. G., Ruttkay-Nedecký, B., Koudelka, H., Bukowska, K., Bursch, W., & Schulte‐Hermann, R. (1995) · Hepatology · doi:10.1002/hep.1840210534 · Cited by 1,223
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 1,188
Organelle isolation: functional mitochondria from mouse liver, muscle and cultured filroblasts
Frezza, C., Cipolat, S., & Scorrano, L. (2007) · Nature Protocols · doi:10.1038/nprot.2006.478 · Cited by 1,188
Self-citationIshihara, 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
Self-citationInhibiting Mitochondrial Fission Protects the Heart Against Ischemia/Reperfusion Injury
Ong, S.-B., Subrayan, S., Lim, S. Y., Yellon, D. M., Davidson, S. M., & Hausenloy, D. J. (2010) · Circulation · doi:10.1161/circulationaha.109.906610 · Cited by 986
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
Narendra, D. P., Kane, L. A., Hauser, D. N., Fearnley, I. M., & Youle, R. J. (2010) · Autophagy · doi:10.4161/auto.6.8.13426 · Cited by 810
Sohal, D. S., Nghiem, M. P., Crackower, M. A., Witt, S. A., Kimball, T. R., Tymitz, K. M., Penninger, J. M., & Molkentin, J. D. (2001) · Circulation Research · doi:10.1161/hh1301.092687 · Cited by 697
Yang, D., Oyaizu, Y., Oyaizu, H., Olsen, G. J., & Woese, C. R. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4443 · Cited by 609
Mitochondrial Fusion is Essential for Organelle Function and Cardiac Homeostasis
Chen, Y., Liu, Y., & Dorn, G. W. (2011) · Circulation Research · doi:10.1161/circresaha.111.258723 · Cited by 515
Self-citationSzabadkai, G., Simoni, A. M., Chami, M., Wieckowski, M. R., Youle, R. J., & Rizzuto, R. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.09.026 · Cited by 468
Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner
Frank, M., Duvezin-Caubet, S., Koob, S., Occhipinti, A., Jagasia, R., Petcherski, A., Ruonala, M. O., Priault, M., Salin, B., & Reichert, A. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.08.007 · Cited by 468
Oka, T., Maillet, M., Watt, A. J., Schwartz, R. J., Aronow, B. J., Duncan, S. A., & Molkentin, J. D. (2006) · Circulation Research · doi:10.1161/01.res.0000215985.18538.c4 · Cited by 424
Parkin‐independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain
Kageyama, Y., Hoshijima, M., Seo, K., Bedja, D., Sysa‐Shah, P., Andrabi, S. A., Chen, W., Höke, A., Dawson, V. L., Dawson, T. M., et al. (2014) · The EMBO Journal · doi:10.15252/embj.201488658 · Cited by 420
Chen, Y., Csordás, G., Jowdy, C. C., Schneider, T. G., Csordás, N., Wang, W., Liu, Y., Kohlhaas, M., Meiser, M., Bergem, S., et al. (2012) · Circulation Research · doi:10.1161/circresaha.112.266585 · Cited by 353
Self-citationDisatnik, M., Ferreira, J. C. B., Campos, J. C., Gomes, M. K., Dourado, P. M. M., Qi, X., & Mochly‐Rosen, D. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000461 · Cited by 340
Mitochondrial myopathy induces a starvation-like response
Tyynismaa, H., Carroll, C. J., Raimundo, N., Ahola-Erkkilä, S., Wenz, T., Ruhanen, H., Guse, K., Hemminki, A., Peltola-Mjøsund, K. E., Tulkki, V., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq310 · Cited by 300
HAMER, P. W., McGeachie, J. K., Davies, M. J., & Grounds, M. D. (2002) · Journal of Anatomy · doi:10.1046/j.0021-8782.2001.00008.x · Cited by 298
Bax regulates primary necrosis through mitochondrial dynamics
Whelan, R. S., Konstantinidis, K., Wei, A.-C., Chen, Y., Reyna, D. E., Jha, S., Yang, Y., Calvert, J. W., Lindsten, T., Thompson, C. B., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201608109 · Cited by 290
Self-citationBaumgartner, H. K., Gerasimenko, J. V., Thorne, C., Ferdek, P. E., Pozzan, T., Tepikin, A. V., Petersen, O. H., Sutton, R., Watson, A. J. M., & Gerasimenko, O. V. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025353 · Cited by 276
Decompensation of Cardiac Hypertrophy: Cellular Mechanisms and Novel Therapeutic Targets
Diwan, A., & Dorn, G. W. (2007) · Physiology · doi:10.1152/physiol.00033.2006 · Cited by 227
Self-citationMitofusins 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 223
Song, M., Chen, Y., Gong, G., Murphy, E., Rabinovitch, P. S., & Dorn, G. W. (2014) · Circulation Research · doi:10.1161/circresaha.115.304384 · Cited by 189
Self-citationMitochondrial dynamics in heart disease
Dorn, G. W. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.03.008 · Cited by 167
Self-citationNix-Mediated Apoptosis Links Myocardial Fibrosis, Cardiac Remodeling, and Hypertrophy Decompensation
Diwan, A., Wansapura, J. P., Syed, F. M., Matkovich, S. J., Lorenz, J. N., & Dorn, G. W. (2008) · Circulation · doi:10.1161/circulationaha.107.727073 · Cited by 164
Self-citationBhandari, P., Song, M., Chen, Y., Burelle, Y., & Dorn, G. W. (2013) · Circulation Research · doi:10.1161/circresaha.114.302734 · Cited by 154
Self-citationBit-by-bit autophagic removal of parkin-labelled mitochondria
Yang, J., & Yang, W. Y. (2013) · Nature Communications · doi:10.1038/ncomms3428 · Cited by 143
Chen, Y., Lewis, W., Diwan, A., Cheng, E. H. Y., Matkovich, S. J., & Dorn, G. W. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914013107 · Cited by 142
Self-citationCyclophilin D is required for mitochondrial removal by autophagy in cardiac cells
Carreira, R., Lee, Y., Ghochani, M., Gustafsson, Å. B., & Gottlieb, R. A. (2010) · Autophagy · doi:10.4161/auto.6.4.11553 · Cited by 131
Ngo, J. K., & Davies, K. J. A. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1404.015 · Cited by 106
Inhibition of Drp1-dependent mitochondrial division impairs myogenic differentiation
Kim, B., Kim, J.-S., Yoon, Y., Santiago, M. C., Brown, M. D., & Park, J. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00502.2012 · Cited by 105
Mitochondrial fragmentation caused by phenanthroline promotes mitophagy
Park, S. J., Shin, J. H., Kim, E. S., Jo, Y. K., Kim, J.-H., Hwang, J. J., Kim, J. C., & Cho, D. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.10.035 · Cited by 67
Martinelli, P., Mattina, V. L., Bernacchia, A., Magnoni, R., Cerri, F., Cox, G. A., Quattrini, A., Casari, G., & Rugarli, E. I. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp124 · Cited by 65
Caffin, F., Prola, A., Piquereau, J., Novotova, M., David, D. J., Garnier, A., Fortin, D., Alavi, M. V., Veksler, V., Ventura‐Clapier, R., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.263079 · Cited by 55
Mitochondrial Dynamism and Cardiac Fate
Dorn, G. W. (2013) · Circulation Journal · doi:10.1253/circj.cj-13-0453 · Cited by 28
Self-citationMitochondrial Genome Linearization Is a Causative Factor for Cardiomyopathy in Mice and Drosophila
Chen, Y., Sparks, M., Bhandari, P., Matkovich, S. J., & Dorn, G. W. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5432 · Cited by 23
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Lopaschuk, G. D., Karwi, Q. G., Tian, R., Wende, A. R., & Abel, E. D. (2021) · Circulation Research · doi:10.1161/circresaha.121.318241 · Cited by 1,458
Distinct fission signatures predict mitochondrial degradation or biogenesis.
Kleele, T., Rey, T., Winter, J., Zaganelli, S., Mahecic, D., Perreten Lambert, H., Ruberto, F. P., Nemir, M., Wai, T., Pedrazzini, T., et al. (2021) · Nature · doi:10.1038/s41586-021-03510-6 · Cited by 794
Mitonuclear communication in homeostasis and stress
Quirós, P. M., Mottis, A., & Auwerx, J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.23 · Cited by 787
Mitophagy, Mitochondrial Homeostasis, and Cell Fate
Ma, K., Chen, G., Li, W., Kepp, O., Zhu, Y., & Chen, Q. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00467 · Cited by 623
“Reports suggested that Drp1mediated mitochondrial fission was dispensable for mitophagy (Song et al., 2015; Yamashita et al., 2016).”
BackgroundBasit, F., van Oppen, L. M. P. E., Schöckel, L., Bossenbroek, H. M., Vries, S. E. V. E., Hermeling, J. C., Grefte, S., Kopitz, C., Héroult, M., Willems, P. H. G. M., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.133 · Cited by 574
Metadata
- Authors
- Song, M., Mihara, K., Chen, Y., Scorrano, L., & Dorn, G. W.
- Affiliations
- Washington University in St. Louis (US)
- Kyushu University (JP)
- University of Padua (IT)
- Corresponding author
- Dorn, Gerald W.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 21
- Issue
- 2
- Pages
- 273-286
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4318753
- OpenAlex
- W2044929466
- Cited by
- 482
- References
- 47
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 51 · 2023: 42 · 2022: 42 · 2021: 63 · 2020: 55 · 2019: 43 · 2018: 39 · 2017: 33 · 2016: 40 · 2015: 21
- FWCI
- 19.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (25291046)
- National Heart, Lung, and Blood Institute (HL59888, R01HL059888)
- 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
- mitochondrial fission, mitochondrial fusion, mitophagy, Drp1, mitofusins, Mfn1, mitofusin 2, mitochondrial quality control, myocardial necrosis, dilated cardiomyopathy, mitochondrial permeability transition pore, unfolded protein response, mitochondrial fragmentation, embryonic fibroblasts, heart
- MeSH terms
- Animals, Cells, Cultured, Fibroblasts, Mice, Transgenic, Mitochondria, Heart, Myocardium, Mice, Knockout, GTP Phosphohydrolases, Dynamins, Mice, Mitochondrial Dynamics, Mitophagy
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