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.
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
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?
Mfn2 has been shown to participate in mitophagy in cardiomyocytes.
“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
Impairment of fission leads to disruption of selective mitochondrial autophagic degradation, followed by dysfunctional organelle accumulation.
“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]
Disrupted mitochondrial fission obtained with specific ablation of DRP1 in the heart induces accumulation of defective mitochondria due to impaired autophagy/mitophagy, which over time promotes cardiomyocyte death.
“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]
Conditional ablation of DRP1 in the heart, brain, and skeletal muscle causes lethality.
“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]
Energy stress consequent to acute or chronic exercise triggers autophagy in different tissues.
“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]
Mitophagy is intricately linked to mitochondrial dynamics.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 5,120 · see citing works
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 · see citing works
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674 · see citing works
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 · see citing works
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 · see citing works
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
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 · see citing works
Self-citationGray, M. W., Burger, G., & Lang, B. F. (1999) · Science · doi:10.1126/science.283.5407.1476 · Cited by 1,710 · see citing works
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 · see citing works
Self-citationOrganelle 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 · see citing works
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 1,167 · 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
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
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 · 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
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 789 · see citing works
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 · see citing works
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 · see citing works
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 506 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 348 · see citing works
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 333 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 224 · see citing works
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 217 · see citing works
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 188 · see citing works
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 168 · see citing works
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 159 · see citing works
Self-citationBhandari, P., Song, M., Chen, Y., Burelle, Y., & Dorn, G. W. (2013) · Circulation Research · doi:10.1161/circresaha.114.302734 · Cited by 153 · see citing works
Self-citationChen, 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 143 · see citing works
Self-citationBit-by-bit autophagic removal of parkin-labelled mitochondria
Yang, J., & Yang, W. Y. (2013) · Nature Communications · doi:10.1038/ncomms3428 · Cited by 140 · see citing works
Cyclophilin 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 127 · see citing works
Ngo, J. K., & Davies, K. J. A. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1404.015 · Cited by 104 · see citing works
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 103 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Mitochondrial Dynamism and Cardiac Fate
Dorn, G. W. (2013) · Circulation Journal · doi:10.1253/circj.cj-13-0453 · Cited by 28 · see citing works
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 · see citing works
Self-citation
Flagged first, then by citations
2 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Cardiac Energy Metabolism in Heart Failure
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 1,420 · see citing works
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 · see citing works
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 · see citing works
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 609 · see citing works
Basit, 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 570 · see citing works
Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice
Wai, T., García-Prieto, J., Baker, M. J., Merkwirth, C., Benit, P., Rustin, P., Rupérez, F. J., Barbas, C., Ibañez, B., & Langer, T. (2015) · Science · doi:10.1126/science.aad0116 · Cited by 551 · see citing works
The Role of Autophagy in the Heart
Sciarretta, S., Maejima, Y., Zablocki, D., & Sadoshima, J. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121427 · Cited by 547 · see citing works
Molecular mechanisms and consequences of mitochondrial permeability transition
Bonora, M., Giorgi, C., & Pinton, P. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00433-y · Cited by 549 · see citing works
Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum–mitochondria tether
Naon, D., Zaninello, M., Giacomello, M., Varanita, T., Grespi, F., Lakshminaranayan, S., Serafini, A., Semenzato, M., Herkenne, S., Hernández-Alvarez, M. I., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606786113 · Cited by 521 · see citing works
Self-citationMitochondrial biogenesis and dynamics in the developing and diseased heart
Dorn, G. W., Vega, R. B., & Kelly, D. P. (2015) · Genes & Development · doi:10.1101/gad.269894.115 · Cited by 470 · see citing works
Self-citationMitochondrial fission facilitates the selective mitophagy of protein aggregates
Burman, J. L., Pickles, S., Wang, C., Sekine, S., Vargas, J. N. S., Zhang, Z., Youle, A. M., Nezich, C. L., Wu, X., Hammer, J. A., et al. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201612106 · Cited by 479 · see citing works
Shirakabe, A., Zhai, P., Ikeda, Y., Saito, T., Maejima, Y., Hsu, C., Nomura, M., Egashira, K., Levine, B., & Sadoshima, J. (2016) · Circulation · doi:10.1161/circulationaha.115.020502 · Cited by 468 · see citing works
Mitochondrial autophagy: molecular mechanisms and implications for cardiovascular disease
Li, A., Gao, M. Q., Liu, B., Qin, Y. H., Chen, L., Liu, H., Wu, H., & Gong, G. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04906-6 · Cited by 469 · see citing works
Mitochondrial ROS in myocardial ischemia reperfusion and remodeling
Bugger, H., & Pfeil, K. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165768 · Cited by 469 · see citing works
Mitochondrial Function, Biology, and Role in Disease
Murphy, E., Ardehali, H., Balaban, R. S., DiLisa, F., Dorn, G. W., Kitsis, R. N., Otsu, K., Ping, P., Rizzuto, R., Sack, M. N., et al. (2016) · Circulation Research · doi:10.1161/res.0000000000000104 · Cited by 459 · see citing works
Self-citationMitochondrial 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
Sebastián, D., Sorianello, E., Segalés, J., Irazoki, A., Ruiz‐Bonilla, V., Sala, D., Planet, E., Berenguer‐Llergo, A., Muñoz, J. P., Sánchez‐Feutrie, M., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201593084 · Cited by 396 · see citing works
Hamacher‐Brady, A., & Brady, N. R. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2087-8 · Cited by 396 · see citing works
Mitochondrial quality control mechanisms as molecular targets in cardiac ageing
Picca, A., Mankowski, R. T., Burman, J. L., Donisi, L., Js, K., Marzetti, E., & Leeuwenburgh, C. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0059-z · Cited by 393 · see citing works
Drp1-dependent mitochondrial fission in cardiovascular disease
Jin, J., Wei, X., Zhi, X., Wang, X., & Meng, D. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00518-y · Cited by 386 · see citing works
Repairing mitochondrial dysfunction in disease
Sorrentino, V., Menzies, K. J., & Auwerx, J. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104908 · Cited by 337 · see citing works
Liu, Y. J., McIntyre, R. L., Janssens, G. E., & Houtkooper, R. H. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111212 · Cited by 334 · see citing works
Mitochondrial quality control mechanisms as molecular targets in cardiac ischemia–reperfusion injury
Wang, J., & Zhou, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.03.004 · Cited by 324 · see citing works
Abrogating Mitochondrial Dynamics in Mouse Hearts Accelerates Mitochondrial Senescence
Song, M., Franco, A., Fleischer, J. A., Zhang, L., & Dorn, G. W. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.023 · Cited by 309 · see citing works
Self-citationMolecular Mechanisms of Mitochondrial Autophagy/Mitophagy in the Heart
Saito, T., & Sadoshima, J. (2015) · Circulation Research · doi:10.1161/circresaha.116.303790 · Cited by 321 · see citing works
Lampert, M. A., Orogo, A. M., Najor, R. H., Hammerling, B. C., Leon, L. J., Wang, B. J., Kim, T.-Y., Sussman, M. A., & Gustafsson, Å. B. (2019) · Autophagy · doi:10.1080/15548627.2019.1580095 · Cited by 314 · see citing works
Mitochondrial dynamics in health and disease
Yapa, N. M. B., Lisnyak, V., Reljić, B., & Ryan, M. T. (2021) · FEBS Letters · doi:10.1002/1873-3468.14077 · Cited by 312 · see citing works
How mitochondrial dynamism orchestrates mitophagy
Shirihai, O. S., Song, M., & Dorn, G. W. (2015) · Circulation Research · doi:10.1161/circresaha.116.306374 · Cited by 311 · see citing works
Self-citationThe role of mitochondrial fission in cardiovascular health and disease
Quiles, J. M., & Gustafsson, Å. B. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00703-y · Cited by 305 · see citing works
Wu, S., Lu, Q., Ding, Y., Wu, Y., Qiu, Y., Wang, P., Mao, X., Huang, K., Xie, Z., & Zou, M.-H. (2019) · Circulation · doi:10.1161/circulationaha.118.033552 · Cited by 298 · see citing works
Yamada, T., Murata, D., Adachi, Y., Itoh, K., Kameoka, S., Igarashi, A., Kato, T., Araki, Y., Huganir, R. L., Dawson, T. M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.014 · Cited by 291 · see citing works
Mitochondrial Dynamics: Coupling Mitochondrial Fitness with Healthy Aging
Sebastián, D., Palacı́n, M., & Antonio Zorzano, A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.01.003 · Cited by 281 · see citing works
Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired
Liang, W., Sagar, S., Ravindran, R., Najor, R. H., Quiles, J. M., Chi, L., Diao, R. Y., Woodall, B. P., Leon, L. J., Zumaya, E., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40680-5 · Cited by 273 · see citing works
Role of mitochondrial quality surveillance in myocardial infarction: From bench to bedside
Zhou, H., Ren, J. T., Toan, S., & Mui, D. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101250 · Cited by 251 · 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
Mitophagy and mitochondrial integrity in cardiac ischemia-reperfusion injury
Yang, M., Linn, B. S., Zhang, Y., & Ren, J. T. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.05.007 · Cited by 250 · see citing works
Correcting mitochondrial fusion by manipulating mitofusin conformations
Franco, A., Kitsis, R. N., Fleischer, J. A., Gavathiotis, E., Kornfeld, O. S., Gong, G., Biris, N., Benz, A. M., Qvit, N., Donnelly, S. K., et al. (2016) · Nature · doi:10.1038/nature20156 · Cited by 241 · see citing works
Self-citationEvolving and Expanding the Roles of Mitophagy as a Homeostatic and Pathogenic Process
Gustafsson, Å. B., & Dorn, G. W. (2018) · Physiological Reviews · doi:10.1152/physrev.00005.2018 · Cited by 229 · see citing works
Self-citationMitochondrial 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
Mitochondrial dynamics as regulators of cancer biology
Trotta, A. P., & Chipuk, J. E. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2451-3 · Cited by 220 · see citing works
A Rab5 endosomal pathway mediates Parkin-dependent mitochondrial clearance
Hammerling, B. C., Najor, R. H., Cortez, M. Q., Shires, S. E., Leon, L. J., Gonzalez, E. R., Boassa, D., Phan, S., Thor, A., Jimenez, R. E., et al. (2017) · Nature Communications · doi:10.1038/ncomms14050 · Cited by 216 · see citing works
Self-citationTahrir, F. G., Langford, D., Amini, S., Ahooyi, T. M., & Khalili, K. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27597 · Cited by 216 · see citing works
The role of mitochondrial dynamics in cardiovascular diseases
Forte, M., Schirone, L., Ameri, P., Basso, C., Catalucci, D., Modica, J., Chimenti, C., Crotti, L., Frati, G., Rubattu, S. D., et al. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15068 · Cited by 221 · see citing works
Mitochondrial Reactive Oxygen Species at the Heart of the Matter
Kornfeld, O. S., Hwang, S., Disatnik, M., Chen, C., Qvit, N., & Mochly‐Rosen, D. (2015) · Circulation Research · doi:10.1161/circresaha.116.305432 · Cited by 210 · see citing works
Yamashita, S.-I., Jin, X., Furukawa, K., Hamasaki, M., Nezu, A., Otera, H., Saigusa, T., Yoshimori, T., Sakai, Y., Mihara, K., et al. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201605093 · Cited by 209 · see citing works
Self-citationInterdependence of Parkin-Mediated Mitophagy and Mitochondrial Fission in Adult Mouse Hearts
Song, M., Gong, G., Burelle, Y., Gustafsson, Å. B., Kitsis, R. N., Matkovich, S. J., & Dorn, G. W. (2015) · Circulation Research · doi:10.1161/circresaha.117.306859 · Cited by 209 · see citing works
Self-citationMitophagy, Mitochondrial Dynamics, and Homeostasis in Cardiovascular Aging
Wu, N. N., Zhang, Y., & Ren, J. T. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9825061 · Cited by 196 · 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
Abdullah, C. S., Alam, S., Aishwarya, R., Miriyala, S., Bhuiyan, M. A. N., Panchatcharam, M., Pattillo, C. B., Orr, A. W., Sadoshima, J., Hill, J. A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-37862-3 · Cited by 195 · see citing works
de Oliveira, M. R., Nabavi, S. F., Manayi, A., Daglia, M., Hajheydari, Z., & Nabavi, S. M. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.01.017 · Cited by 192 · see citing works
Ahola, S., Rivera-Mejías, P., Hermans, S., Chandragiri, S., Giavalisco, P., Nolte, H., & Langer, T. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.017 · Cited by 191 · see citing works
Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction
Hall, A. R., Burke, N., Dongworth, R. K., Kalkhoran, S. B., Dyson, A., Vicencio, J. M., Dorn, G. W., Yellon, D. M., & Hausenloy, D. J. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.139 · Cited by 190 · see citing works
Self-citationMitochondrial quality control mechanisms as molecular targets in diabetic heart
Chang, X., Li, Y., Cai, C., Wu, F., He, J., Zhang, Y., Zhong, J., Tan, Y., Liu, R., Zhu, H., et al. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155313 · Cited by 192 · see citing works
Evolving Concepts of Mitochondrial Dynamics
Dorn, G. W. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114358 · Cited by 187 · see citing works
Self-citationMitophagy-dependent macrophage reprogramming protects against kidney fibrosis
Bhatia, D., Chung, K.-P., Nakahira, K., Patino, E., Rice, M. C., Torres, L. K., Muthukumar, T., Choi, A. M. K., Akchurin, O. M., & Choi, M. E. (2019) · JCI Insight · doi:10.1172/jci.insight.132826 · Cited by 185 · see citing works
The ever-growing complexity of the mitochondrial fission machinery
Pagliuso, A., Cossart, P., & Stavru, F. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2603-0 · Cited by 184 · see citing works
Mitofusins regulate lipid metabolism to mediate the development of lung fibrosis
Chung, K., Hsu, C., Fan, L.-C., Huang, Z., Bhatia, D., Chen, Y., Hisata, S., Cho, S. J., Nakahira, K., Imamura, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11327-1 · Cited by 179 · see citing works
Self-citationSarcoplasmic reticulum–mitochondria communication in cardiovascular pathophysiology
López‐Crisosto, C., Pennanen, C., Vásquez-Trincado, C., Morales, P. E., Bravo, R., Quest, A. F. G., Chiong, M., & Lavandero, S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.23 · Cited by 183 · see citing works
Emerging role of mitophagy in cardiovascular physiology and pathology
Morales, P. E., Arias-Durán, C., Ávalos-Guajardo, Y., Aedo, G., Verdejo, H., Parra, V., & Lavandero, S. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.09.006 · Cited by 178 · see citing works
Ayanga, B. A., Badal, S. S., Wang, Y., Galvan, D. L., Chang, B. H., Schumacker, P. T., & Danesh, F. R. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015101096 · Cited by 174 · see citing works
Mitochondrial quality control: from molecule to organelle
Roca-Portoles, A., & Tait, S. W. G. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03775-0 · Cited by 174 · see citing works
Titration of mitochondrial fusion rescues <i>Mff</i> -deficient cardiomyopathy
Chen, H., Ren, S., Clish, C., Jain, M., Mootha, V., McCaffery, J. M., & Chan, D. C. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201507035 · Cited by 168 · see citing works
Mitohormesis, an Antiaging Paradigm
Bárcena, C., Mayoral, P., & Quirós, P. M. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.05.002 · Cited by 167 · see citing works
Heme oxygenase-1 regulates mitochondrial quality control in the heart
Hull, T. D., Boddu, R., Guo, L., Tisher, C. C., Traylor, A., Patel, B., Joseph, R., Prabhu, S. D., Suliman, H. B., Piantadosi, C. A., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.85817 · Cited by 171 · see citing works
Mitochondrial dynamics and cell death in heart failure
Marı́n-Garcı́a, J., & Akhmedov, A. T. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9530-2 · Cited by 154 · see citing works
Cellular Allometry of Mitochondrial Functionality Establishes the Optimal Cell Size
Miettinen, T. P., & Björklund, M. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.09.004 · Cited by 156 · see citing works
Advances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond
Sun, Q., Karwi, Q. G., Wong, N. K. P., & Lopaschuk, G. D. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae231 · Cited by 160 · see citing works
Pernas, L., Bean, C., Boothroyd, J. C., & Scorrano, L. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.018 · Cited by 144 · see citing works
Self-citationJong, K. A. D., & Lopaschuk, G. D. (2017) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.03.009 · Cited by 148 · see citing works
Mitochondrial function in the heart: the insight into mechanisms and therapeutic potentials
Nguyen, B. Y., Ruiz‐Velasco, A., Bùi, T. A., Collins, L., Wang, X., & Liu, W. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14431 · Cited by 151 · see citing works
Mitochondrial dynamism and heart disease: changing shape and shaping change
Dorn, G. W. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404575 · Cited by 147 · see citing works
Self-citationMolecular regulation of mitochondrial dynamics in cardiac disease
Nan, J., Zhu, W. M., Rahman, M. S. U., Liu, M., Li, D. X., Su, S., Zhang, N., Hu, X., Yu, H., Gupta, M. P., et al. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.03.006 · Cited by 146 · see citing works
Wang, H., Chen, S., Zhang, Y., Xu, H., & Sun, H. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.07.004 · Cited by 145 · see citing works
Li, E., Li, X., Huang, J., Xu, C., Liang, Q., Ren, K., Bai, A., Lü, C., Qian, R., & Sun, N. (2020) · Protein & Cell · doi:10.1007/s13238-020-00713-x · Cited by 142 · see citing works
Manna, S., McCarthy, C., & McCarthy, F. P. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/3095383 · Cited by 141 · see citing works
Mitochondrial quality surveillance as a therapeutic target in myocardial infarction
Zhu, H., Toan, S., Mui, D., & Zhou, H. (2020) · Acta Physiologica · doi:10.1111/apha.13590 · Cited by 142 · see citing works
Novel targets for mitochondrial medicine
Wang, W., Karamanlidis, G., & Tian, R. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aac7410 · Cited by 138 · see citing works
Mitochondria as a therapeutic target for cardiac ischemia‑reperfusion injury (Review)
Marin, W., Marin, D., Ao, X., & Liu, Y. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4823 · Cited by 138 · see citing works
Nishimura, A., Shimauchi, T., Tanaka, T., Shimoda, K., Toyama, T., Kitajima, N., Ishikawa, T., Shindo, N., Numaga‐Tomita, T., Yasuda, S., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aat5185 · Cited by 135 · see citing works
Yan, T., & Zhao, Y. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101381 · Cited by 137 · see citing works
Physiological Mitochondrial Fragmentation Is a Normal Cardiac Adaptation to Increased Energy Demand
Coronado, M. J., Fajardo, G., Nguyen, K., Zhao, M., Kooiker, K. B., Jung, G., Hu, D., Reddy, S., Sandoval, E., Stotland, A. B., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.310725 · Cited by 134 · see citing works
Garbern, J. C., & Lee, R. T. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02252-6 · Cited by 144 · see citing works
Mitoconfusion: Noncanonical Functioning of Dynamism Factors in Static Mitochondria of the Heart
Song, M., & Dorn, G. W. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.019 · Cited by 127 · see citing works
Self-citationMitophagy-driven metabolic switch reprograms stem cell fate
Naik, P. P., Birbrair, A., & Bhutia, S. K. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2922-9 · Cited by 130 · see citing works
Huang, Y., Zhou, J., Wang, S., Xiong, J., Chen, Y., Liu, Y., Xiao, T., Li, Y., He, T., Li, Y., et al. (2020) · Theranostics · doi:10.7150/thno.45455 · Cited by 128 · see citing works
Self-citationKoch, J., Feichtinger, R. G., Freisinger, P., Pies, M., Schrödl, F., Iuso, A., Sperl, W., Mayr, J. A., Prokisch, H., & Haack, T. B. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103500 · Cited by 127 · see citing works
Grel, H., Woźnica, D., Ratajczak, K., Kalwarczyk, E., Anchimowicz, J., Świtlik, W. Z., Olejnik, P., Zielonka, P., Stobiecka, M., & Jakieła, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713033 · Cited by 129 · see citing works
Targeting the Mitochondria in Heart Failure
Sabbah, H. N. (2020) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2019.07.009 · Cited by 123 · see citing works
Mammalian mitophagy – from in vitro molecules to in vivo models
Rodger, C. E., McWilliams, T. G., & Ganley, I. G. (2017) · FEBS Journal · doi:10.1111/febs.14336 · Cited by 121 · see citing works
Mitochondrial Biogenesis, Mitochondrial Dynamics, and Mitophagy in the Maturation of Cardiomyocytes
Ding, Q., Qi, Y., & Tsang, S. Y. (2021) · Cells · doi:10.3390/cells10092463 · Cited by 122 · see citing works
Mitophagy for cardioprotection
Titus, A. S., Sung, E., Zablocki, D., & Sadoshima, J. (2023) · Basic Research in Cardiology · doi:10.1007/s00395-023-01009-x · Cited by 121 · see citing works
Adaniya, S. M., O‐Uchi, J., Cypress, M. W., Kusakari, Y., & Jhun, B. S. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00523.2018 · Cited by 115 · see citing works
Physical Exercise: A Novel Tool to Protect Mitochondrial Health
Sorriento, D., Di Vaia, E., & Iaccarino, G. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.660068 · Cited by 118 · see citing works
Mitochondrial Dynamics in Adult Cardiomyocytes and Heart Diseases
Li, A., Gao, M., Jiang, W., Qin, Y. H., & Gong, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.584800 · Cited by 116 · see citing works
The Role of Impaired Mitochondrial Dynamics in MFN2-Mediated Pathology
Zaman, M., & Shutt, T. E. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.858286 · Cited by 113 · see citing works
Targeting mitochondrial fusion and fission proteins for cardioprotection
Hernández‐Reséndiz, S., Prunier, F., Girão, H., Dorn, G. W., Hausenloy, D. J., & (CA16225), E. C. A. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15384 · Cited by 110 · see citing works
Self-citationWang, S., Tan, J., Miao, Y., & Zhang, Q. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.848214 · Cited by 110 · see citing works
Ishikita, A., Matoba, T., Ikeda, G., Koga, J., Mao, Y., Nakano, K., Takeuchi, O., Sadoshima, J., & Egashira, K. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003872 · Cited by 106 · see citing works
Xiong, W., Ma, Z., An, D., Liu, Z., Cai, W., Bai, Y., Zhan, Q., Lai, W., Zeng, Q., Ren, H., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00411 · Cited by 100 · see citing works
Curcumin, mitochondrial biogenesis, and mitophagy: Exploring recent data and indicating future needs
de Oliveira, M. R., Jardim, F. R., Setzer, W. N., Nabavi, S. M., & Nabavi, S. F. (2016) · Biotechnology Advances · doi:10.1016/j.biotechadv.2016.04.004 · Cited by 100 · see citing works
- 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
- Health Sciences › Medicine › Epidemiology › 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
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
