Cited by 1,196Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

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Fusion and Fission: Interlinked Processes Critical for Mitochondrial Health

Chan, David C.·2012·Annual Review of Genetics

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Abstract

Mitochondria are dynamic organelles that continually undergo fusion and fission. These opposing processes work in concert to maintain the shape, size, and number of mitochondria and their physiological function. Some of the major molecules mediating mitochondrial fusion and fission in mammals have been discovered, but the underlying molecular mechanisms are only partially unraveled. In particular, the cast of characters involved in mitochondrial fission needs to be clarified. By enabling content mixing between mitochondria, fusion and fission serve to maintain a homogeneous and healthy mitochondrial population. Mitochondrial dynamics has been linked to multiple mitochondrial functions, including mitochondrial DNA stability, respiratory capacity, apoptosis, response to cellular stress, and mitophagy. Because of these important functions, mitochondrial fusion and fission are essential in mammals, and even mild defects in mitochondrial dynamics are associated with disease. A better understanding of these processes likely will ultimately lead to improvements in human health.

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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
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Tait, S. W. G., & Green, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2952 · Cited by 2,593
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de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
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Friedman, J. R., Lackner, L. L., West, M., DiBenedetto, J. R., Nunnari, J., & Voeltz, G. K. (2011) · Science · doi:10.1126/science.1207385 · Cited by 2,072
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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
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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
During autophagy mitochondria elongate, are spared from degradation and sustain cell viability
Gomes, L. C., Benedetto, G. D., & Scorrano, L. (2011) · Nature Cell Biology · doi:10.1038/ncb2220 · Cited by 1,735

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Background
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BackgroundInfluential
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Bravo, R., Parra, V., López‐Crisosto, C., Díaz, P., Quest, A. F. G., & Lavandero, S. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160013 · Cited by 304
“Drp-1 is recruited and regulated by other mitochondrial fission proteins, including Mff, MiD49, MiD51, and Fis-1 (12,67,74) (Fig.”
Influential
Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential
Luchsinger, L. L., de Almeida, M. J., Corrigan, D., Mumau, M. D., & Snoeck, H. (2016) · Nature · doi:10.1038/nature16500 · Cited by 247
Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline
Lieber, T., Jeedigunta, S. P., Palozzi, J. M., Lehmann, R., & Hurd, T. R. (2019) · Nature · doi:10.1038/s41586-019-1213-4 · Cited by 242
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
Mitochondrial Biogenesis: A Therapeutic Target for Neurodevelopmental Disorders and Neurodegenerative Diseases
Uittenbogaard, M. N., & Chiaramello, A. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140305224906 · Cited by 246
The Key Roles of GSK-3β in Regulating Mitochondrial Activity
Yang, K. H., Chen, Z., Gao, J., Shi, W., Li, L., Jiang, S., Hu, H., Liu, Z., Xu, D., & Wu, L. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000485580 · Cited by 241
Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia
Perdomini, M., Belbellaa, B., Monassier, L., Reutenauer, L., Messaddeq, N., Cartier, N., Crystal, R. G., Aubourg, P. R., & Puccio, H. M. (2014) · Nature Medicine · doi:10.1038/nm.3510 · Cited by 250
Mitochondria in the signaling pathways that control longevity and health span
Akbari, M., Kirkwood, T. B. L., & Bohr, V. A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100940 · Cited by 234
“The central fission proteins include the dynamin-related protein 1 (DRP1), mitochondrial fission factor (MFF), mitochondrial fission 1 protein (Fis1), and mitochondrial dynamic proteins MiD49, and MiD51 (Chan, 2012; Loson et al., 2013).”
Mitochondria impact brain function and cognition
Picard, M. A., & McEwen, B. S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321881111 · Cited by 230
Mitochondria in cancer
Grasso, D., Zampieri, L. X., Capelôa, T., de Velde, J. A. V., & Sonveaux, P. (2020) · Cell Stress · doi:10.15698/cst2020.06.221 · Cited by 239
Mitochondrial diseases: from molecular mechanisms to therapeutic advances
Wen, H., Deng, H., Li, B., Chen, J., Zhu, J., Zhang, X., Yoshida, S., & Zhou, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02044-3 · Cited by 284
Mitochondrial Structure and Function in Human Heart Failure
Hinton, A. O., Jr., Claypool, S. M., Neikirk, K., Senoo, N., Wanjalla, C. N., Kirabo, A., & Williams, C. R. (2024) · Circulation Research · doi:10.1161/circresaha.124.323800 · Cited by 239
“Mitochondrial dynamics refers to the coordinated, continuous cycles of fusion and fission 85–87 as mitochondria respond to the changing energy demands of the cell.”
Background
Enzymatic Noncovalent Synthesis
He, H., Tan, W., Guo, J., Yi, M., Shy, A. N., & Xu, B. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00306 · Cited by 225
Altered Myocardial Calcium Cycling and Energetics in Heart Failure—A Rational Approach for Disease Treatment
Gorski, P. A., Ceholski, D. K., & Hajjar, R. J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.01.005 · Cited by 213
“Mitochondria are dynamic organelles that continuously undergo fission and fusion, and these processes are indispensable to their proper function within the cell (Chan, 2012).”
Berberine Protects Glomerular Podocytes via Inhibiting Drp1-Mediated Mitochondrial Fission and Dysfunction
Qin, X., Zhao, Y. S., Gong, J., Huang, W., Su, H., Yuan, F., Fang, K., Wang, D., Li, J., Zou, X., et al. (2019) · Theranostics · doi:10.7150/thno.30640 · Cited by 215
“Mitochondrial fission regulates mitochondrial biogenesis and mitophagy, whereas mitochondrial fusion controls proper distribution of mitochondrial DNA (mtDNA) and metabolic substance across all mitochondria[1, 2].”
Background
1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells
Ryan, Z. C., Craig, T. A., Folmes, C. D. L., Wang, X., Lanza, I. R., Schaible, N., Salisbury, J. L., Nair, K. S., Terzic, A., Sieck, G. C., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.684399 · Cited by 219
“Indeed, there are appropriate increases and decreases in mediators of mitochondrial fusion (OPA1) and fission (Fis1 and Drp1) that are consistent with the observed changes in mitochondrial morphology (59, 60, 62).”
Result
Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy
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
Mitochondrial division and fusion in metabolism
Roy, M., Reddy, P. H., Iijima, M., & Sesaki, H. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.02.001 · Cited by 215
“Defects in the core components of these systems, three dynamin-related GTPases, give rise to several disease conditions, including neonatal death with severe neural defects (defects in outer membrane protein Drp1, which mediates division), Charcot-Marie-Tooth neuropathy type 2A, a neurodegenerative disease of peripher…”
S -nitrosylation drives cell senescence and aging in mammals by controlling mitochondrial dynamics and mitophagy
Rizza, S., Cardaci, S., Montagna, C., Giacomo, G. D., Zio, D. D., Bordi, M., Maiani, E., Campello, S., Borreca, A., Puca, A. A., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1722452115 · Cited by 208
The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering
Ottolini, D., Calí, T., Negro, A., & Brini, M. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt068 · Cited by 210
“Finally, to assess whether DJ-1 or p53 action was related to changes in the expression levels or in the activity of protein regulating both mitochondrial morphology and ER–mitochondria tethering, the levels of expression of Drp1 and Mnf2, both implicated in regulating mitochondria shape and dynamics (45), were quantif…”
Method
The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues
Goetzman, E. S., & Prochownik, E. V. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00129 · Cited by 199
“Both fusion and fission can exert significant influence upon mitochondrial energy production and cell survival (176, 178, 179).”
Background
Transition of acute kidney injury to chronic kidney disease: role of metabolic reprogramming
Zhu, Z., Hu, J., Chen, Z., Feng, J., Yang, X., Liang, W., & Ding, G. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155194 · Cited by 204
Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke
Jurcău, A., & Ardelean, A. I. (2022) · Biomedicines · doi:10.3390/biomedicines10030574 · Cited by 204
Altered brain energetics induces mitochondrial fission arrest in Alzheimer’s Disease
Zhang, L., Trushin, S., Christensen, T. A., Bachmeier, B. V., Gateno, B., Schroeder, A., Yao, J., Itoh, K., Sesaki, H., Poon, W. W., et al. (2016) · Scientific Reports · doi:10.1038/srep18725 · Cited by 201
“5 L/min of CO2 for 30 sec; (2) wait for 40 sec; (3) 10 L/min of CO2 for 60 sec; (4) wait for 3 min.”
Method
Cigarette smoke-induced mitochondrial fragmentation and dysfunction in human airway smooth muscle
Aravamudan, B., Kiel, A., Freeman, M., Delmotte, P., Thompson, M., Vassallo, R., Sieck, G. C., Pabelick, C. M., & Prakash, Y. S. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00155.2013 · Cited by 192
Mitochondrial dynamics and viral infections: A close nexus
Khan, M. A., Syed, G. H., Kim, S., & Siddiqui, A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.12.040 · Cited by 195
“OPA1 is considered a multifunctional protein with pivotal roles in mitochondrial cristae architecture, mitochondrial bioenergetics and apoptosis [13,31].”
Background
Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer's disease
Zhang, L., Zhao, P., Yue, C., Jin, Z., Liu, Q., Du, X., & He, Q. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.01.037 · Cited by 196
Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy
Lee, Y. H., Kim, S. H., Kang, J. M., Heo, J. H., Kim, D.-J., Park, S. H., Sung, M. J., Kim, J., Oh, J., Yang, D. H., et al. (2019) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00565.2018 · Cited by 192
Evolving Concepts of Mitochondrial Dynamics
Dorn, G. W. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114358 · Cited by 197
Dysregulated Mitochondrial Dynamics and Metabolism in Obesity, Diabetes, and Cancer
Dai, W., & Jiang, L. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00570 · Cited by 186
“Mutations in some mitochondrial genes have been demonstrated to be the main causes of these metabolic diseases, such as Charcot–Marie– Tooth disease (Mfn2 mutation) and dominant optic atrophy (Opa1 mutation) (4).”
The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy
Wu, H., Xue, D., Chen, G., Han, Z., Huang, L., Zhu, C., Wang, X., Jin, H., Wang, J., Zhu, Y., et al. (2014) · Autophagy · doi:10.4161/auto.29568 · Cited by 186
Mitochondrial Function in Sepsis
Arulkumaran, N., Deutschman, C. S., Pinsky, M. R., Zuckerbraun, B. S., Schumacker, P. T., Gómez, H., Gómez, A., Murray, P. T., & Kellum, J. A. (2016) · Shock · doi:10.1097/shk.0000000000000463 · Cited by 199
“Mitochondrial fission and fusion responses are dynamic morphological changes that occur in the mitochondrial network (66).”
Stress-responsive regulation of mitochondria through the ER unfolded protein response
Rainbolt, T. K., Saunders, J. M., & Wiseman, R. L. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.06.007 · Cited by 188
The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1
Liu, R., & Chan, D. C. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-08-0591 · Cited by 193
“These processes are essential for maintaining mitochondrial health and function and have important roles in mitochondrial DNA stability and inheritance, respiratory capacity, apoptosis, and mitophagy (Westermann, 2010; Chan, 2012; Youle and van der Bliek, 2012).”

Authors: Chan, D. C.
Affiliations: California Institute of Technology (US)
Corresponding author: Chan, David C.
ORCID: Chan, David C.
Venue: Annual Review of Genetics
Publisher: Annual Reviews
Published: 2012-12-15
Volume: 46
Issue: 1
Pages: 265-287
ISSN: 0066-4197 (ISSN-L)
1545-2948
DOI: 10.1146/annurev-genet-110410-132529
OpenAlex: W2157334943
Cited by: 1,196
References: 141
Citations by year: 2026: 56 · 2025: 45 · 2024: 73 · 2023: 97 · 2022: 94 · 2021: 109 · 2020: 110 · 2019: 102 · 2018: 96 · 2017: 93 · 2016: 89 · 2015: 100 · 2014: 76 · 2013: 53 · 2012: 2
FWCI: 3.80
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Genetics (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health
National Institute of General Medical Sciences (R01GM062967, GM083121, GM062967, R01GM083121)
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 fusion, mitochondrial fission, mitochondrial dynamics, mitochondrial morphology, mitochondrial DNA stability, respiratory capacity, apoptosis, cellular stress response, mitophagy, mitochondrial disease
MeSH terms: Animals, DNA, Mitochondrial, Humans, Membrane Proteins, Mitochondria, Mitosis, Mutation, Apoptosis, GTP Phosphohydrolases, Mitochondrial Diseases, Dynamins, Mitochondrial Membranes, Mice, Mitochondrial Size, Mitochondrial Turnover

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Fusion and Fission: Interlinked Processes Critical for Mitochondrial Health

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