Preventing Mitochondrial Fission Impairs Mitochondrial Function and Leads to Loss of Mitochondrial DNA
Open accessAbstract
Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, the role of mitochondrial fission in homeostasis of the organelle is still unknown. Here we report that preventing mitochondrial fission, by down-regulating expression of Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of mitochondrial respiration coupled to an increase in the levels of cellular reactive oxygen species (ROS). At the cellular level, mitochondrial dysfunction resulting from the lack of fission leads to a drop in the levels of cellular ATP, an inhibition of cell proliferation and an increase in autophagy. In conclusion, we propose that mitochondrial fission is required for preservation of mitochondrial function and thereby for maintenance of cellular homeostasis.
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?
Lack of fission by downregulation of Drp1 expression leads to loss of mitochondrial DNA and a decrease in mitochondrial respiration in HeLa cells.
“Lack of fission by downregulation of Drp1 expression leads to loss of mitochondrial DNA (mtDNA) and a decrease in mitochondrial respiration in HeLa cells (33).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [33]
Depletion of Drp1 in HeLa cells results in mitochondrial dysfunction owing to a loss of mtDNA, suggesting that Drp1 is important for mitochondrial inheritance during cell division and for mitochondrial function.
“Interestingly, depletion of Drp1 in HeLa cells also results in mitochondrial dysfunction owing to a loss of mtDNA, suggesting that Drp1 is also important for mitochondrial inheritance during cell division, as well as for mitochondrial function (Parone et al., 2008).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Parone et al., 2008
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
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214 · see citing works
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · see citing works
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295 · 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
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
Extension of murine life span by overexpression of catalase targeted to mitochondria
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724 · 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
Selective degradation of mitochondria by mitophagy
Kim, I., Rodriguez-Enriquez, S., & Lemasters, J. J. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.034 · Cited by 1,558 · see citing works
Reactive Oxygen Species (Ros-Induced) Ros Release
Zorov, D. B., Filburn, C. R., Klotz, L.-O., Zweier, J. L., & Sollott, S. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1001 · Cited by 1,412 · 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 · cited 1× · see citing works
“electron transfer chain (ETC; [14]) and to reduce mitochondrial”
BackgroundAlexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., et al. (2000) · Nature Genetics · doi:10.1038/79944 · Cited by 1,330 · see citing works
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 · 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
Bereiter‐Hahn, J., & Vöth, M. (1994) · Microscopy Research and Technique · doi:10.1002/jemt.1070270303 · Cited by 900 · see citing works
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 · 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
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 · see citing works
Role of mitochondria in oxidative stress and ageing
Lenaz, G. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00120-0 · Cited by 650 · see citing works
Mitochondrial bioenergetics and structural network organization
Benard, G., Bellance, N., James, D., Parrone, P., Fernandez, H., Letellier, T., & Rossignol, R. (2007) · Journal of Cell Science · doi:10.1242/jcs.03381 · Cited by 618 · see citing works
Self-citationMitochondrial 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
Role of Mitochondria in Oxidative Stress and Aging
Lenaz, G., Bovina, C., D’Aurelio, M., Fato, R., Formiggini, G., Genova, M. L., GIULIANO, G., Pich, M. M., Paolucci, U., Castelli, G. P., et al. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02094.x · Cited by 489 · see citing works
Szabadkai, 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
Pich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., & Zorzano, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi149 · Cited by 455 · 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
Composition and dynamics of human mitochondrial nucleoids.
Garrido, N., Griparić, L., Jokitalo, E., Wartiovaara, J., van der Bliek, A. M., & Spelbrink, J. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-07-0399 · Cited by 390 · see citing works
Organization and dynamics of human mitochondrial DNA
Legros, F., Malka, F., Frachon, P., Lombès, A., & Rojo, M. (2004) · Journal of Cell Science · doi:10.1242/jcs.01134 · Cited by 383 · see citing works
Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology
Stojanovski, D., Koutsopoulos, O. S., Okamoto, K., & Ryan, M. T. (2004) · Journal of Cell Science · doi:10.1242/jcs.01058 · Cited by 332 · see citing works
Estaquier, J., & Arnoult, D. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402107 · Cited by 330 · see citing works
DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans
Jagasia, R., Grote, P., Westermann, B., & Conradt, B. (2005) · Nature · doi:10.1038/nature03316 · Cited by 319 · see citing works
Yoon, Y., Yoon, D., Lim, I. K., Yoon, S., Chung, H., Rojo, M., Malka, F., Jou, M., Martinou, J., & Yoon, G. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20753 · Cited by 275 · see citing works
Self-citationTransfection of adherent and suspended cells by calcium phosphate
Jordan, M. (2004) · Methods · doi:10.1016/j.ymeth.2003.11.011 · Cited by 238 · see citing works
Arnoult, D., Rismanchi, N., Grodet, A., Roberts, R. G., Seeburg, D. P., Estaquier, J., Sheng, M., & Blackstone, C. D. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.041 · Cited by 234 · see citing works
Inhibiting the Mitochondrial Fission Machinery Does Not Prevent Bax/Bak-Dependent Apoptosis
Parone, P. A., James, D. I., Cruz, S. D., Mattenberger, Y., Donzé, O., Barja, F., & Martinou, J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02282-05 · Cited by 231 · see citing works
Self-citationTolkovsky, A. M., Xue, L., Fletcher, G. C., & Borutaite, V. (2002) · Biochimie · doi:10.1016/s0300-9084(02)01371-8 · Cited by 203 · see citing works
Ca2+ Homeostasis during Mitochondrial Fragmentation and Perinuclear Clustering Induced by hFis1
Frieden, M., James, D. I., Castelbou, C., Danckaert, A., Martinou, J., & Demaurex, N. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312366200 · Cited by 203 · see citing works
Self-citationWallace, D. C. (2005) · Gene · doi:10.1016/j.gene.2005.05.001 · Cited by 199 · see citing works
Role for CED-9 and Egl-1 as Regulators of Mitochondrial Fission and Fusion Dynamics
Delivani, P., Adrain, C., Taylor, R. C., Duriez, P. J., & Martin, S. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.034 · Cited by 193 · see citing works
Thread-grain transition of mitochondrial reticulum as a step of mitoptosis and apoptosis
Skulachev, V. P., Bakeeva, L. E., Chernyak, B. V., Domnina, L. V., Minin, A. А., Pletjushkina, O. Y., Saprunova, V. B., Skulachev, I. V., Tsyplenkova, V. G., Vasiliev, J. M., et al. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/b:mcbi.0000009880.94044.49 · Cited by 150 · see citing works
Mitochondrial morphology is dynamic and varied
Rube, D. A., & van der Bliek, A. M. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/b:mcbi.0000009879.01256.f6 · Cited by 123 · see citing works
den Bogert, C. V., Muus, P., Haanen, C., Pennings, A. H. M., Melis, T. E., & Kroon, A. M. (1988) · Experimental Cell Research · doi:10.1016/0014-4827(88)90385-0 · Cited by 57 · see citing works
Regulation of the cell cycle in response to inhibition of mitochondrial generated energy
Gemin, A., Sweet, S., Preston, T. J., & Singh, G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.05.061 · Cited by 43 · see citing works
Radical Metabolism Is Partner to Energy Metabolism in Mitochondria
Xu, J.-X. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.006 · Cited by 24 · see citing works
Yoon, Y., Cho, H., Lee, J., & Yoon, G. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.013 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Mitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803 · see citing works
Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure
Liesa, M., & Shirihai, O. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.002 · Cited by 1,341 · 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
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 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
Jheng, H.-F., Tsai, P.-J., Guo, S.-M., Kuo, L.-H., Chang, C.-S., Su, I.-J., Chang, C.-R., & Tsai, Y.-S. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05603-11 · Cited by 650 · see citing works
The role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551 · 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
Pharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383 · see citing works
Tau Promotes Neurodegeneration via DRP1 Mislocalization In Vivo
DuBoff, B., Götz, J., & Feany, M. B. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.026 · Cited by 377 · 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
Ban-Ishihara, R., Ishihara, T., Sasaki, N., Mihara, K., & Ishihara, N. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301951110 · Cited by 231 · see citing works
Hong, X., Isern, J., Campanario, S., Perdiguero, E., Ramírez-Pardo, I., Segalés, J., Hernansanz-Agustín, P., Curtabbi, A., Deryagin, O., Pollán, A., et al. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.07.009 · Cited by 213 · see citing works
Smits, P., Smeitink, J., & van den Heuvel, L. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/737385 · Cited by 202 · see citing works
Inhibition of mitochondrial fission favours mutant over wild-type mitochondrial DNA
Malena, A., Loro, E., Di Re, M., Holt, I. J., & Vergani, L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp281 · Cited by 107 · see citing works
Cahill, T. J., Leo, V., Kelly, M., Stockenhuber, A., Kennedy, N. W., Bao, L., Cereghetti, G., Harper, A. R., Czibik, G., Lao, C., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.665695 · Cited by 66 · see citing works
Mitochondrial dynamics in skeletal muscle insulin resistance and type 2 diabetes
Fealy, C. E., Mulya, A., Axelrod, C. L., & Kirwan, J. P. (2018) · Translational Research · doi:10.1016/j.trsl.2018.07.011 · Cited by 63 · see citing works
Kitaoka, Y., Ogasawara, R., Tamura, Y., Fujita, S., & Hatta, H. (2015) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2015-0184 · Cited by 54 · see citing works
Jhun, B. S., Lee, H., Jin, Z.-G., & Yoon, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060810 · Cited by 49 · see citing works
Facts and controversies in our understanding of how caloric restriction impacts the mitochondrion
Gouspillou, G., & Hepple, R. T. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.03.004 · Cited by 42 · see citing works
Adlimoghaddam, A., Odero, G. G., Glazner, G., Turner, R. S., & Albensi, B. C. (2021) · Aging and disease · doi:10.14336/ad.2020.0910 · Cited by 38 · see citing works
Cahill, T. J., Leo, V., Kelly, M., Stockenhuber, A., Kennedy, N. W., Bao, L., Cereghetti, G. M., Harper, A. R., Czibik, G., Liao, C., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.a115.665695 · Cited by 14 · see citing works
“Drp1 C452F leads to profound ATP deficiency in MEFs and the Python heart, supporting a wider body of work linking Drp1 with respiratory failure in both cell models and in the heart (36, 38, 41).”
Background
- Authors
- Parone, P. A., Da Cruz, S., Tondera, D., Mattenberger, Y., James, D. I., Maechler, P., Barja, F., & Martinou, J.-C.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Martinou, Jean-Claude
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-09-22
- Volume
- 3
- Issue
- 9
- Pages
- e3257
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2532749
- OpenAlex
- W2018019380
- Cited by
- 415
- References
- 46
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 16 · 2023: 13 · 2022: 15 · 2021: 27 · 2020: 25 · 2019: 19 · 2018: 31 · 2017: 25 · 2016: 19 · 2015: 27 · 2014: 31 · 2013: 42 · 2012: 40
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (109419, 3100A0-109419/1, 3100A0)
- Oncosuisse
- 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, Drp1, mitochondrial DNA loss, mitochondrial respiration, reactive oxygen species, mitochondrial dysfunction, ATP depletion, cell proliferation, autophagy, mitochondrial dynamics, cellular homeostasis
- MeSH terms
- Adenosine Triphosphate, Autophagy, DNA, Mitochondrial, Gene Expression Regulation, HeLa Cells, Homeostasis, Humans, Microtubule-Associated Proteins, Mitochondria, Models, Biological, Oxygen Consumption, Reactive Oxygen Species, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, RNA Interference, Cell Proliferation, Membrane Potential, Mitochondrial
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
