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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“Since mitochondria fusion and fission are strictly related, the activation of one of these processes leads to the inhibition of the other [39].”
Background
CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum-mitochondria signaling
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Dietary zinc deficiency disrupts skeletal muscle proteostasis and mitochondrial biology in rats
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“Mitochondria are highly dynamic entities and continuously go through rapid and opposing processes of fission and fusion [37, 38].”
Background
Mitochondrial dysfunction in the offspring of obese mothers and it's transmission through damaged oocyte mitochondria: Integration of mechanisms
Elías‐López, A. L., Vázquez-Mena, Ó., & Sferruzzi-Perri, A. N. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166802 · Cited by 26
Inhibition of PDGFRβ alleviates endothelial cell apoptotic injury caused by DRP-1 overexpression and mitochondria fusion failure after mitophagy
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TGF ‐β3 mediates mitochondrial dynamics through the p‐Smad3 / AMPK pathway
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Rev1 contributes to proper mitochondrial function via the PARP-NAD+-SIRT1-PGC1α axis
Fakouri, N. B., Durhuus, J. A., Regnell, C. E., Angleys, M., Desler, C., Hasan‐Olive, M. M., Martín-Pardillos, A., Tsaalbi‐Shtylik, A., Thomsen, K., Lauritzen, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-12662-3 · Cited by 24
The GTPase domain of gamma-tubulin is required for normal mitochondrial function and spatial organization
Lindström, L., Li, T., Malycheva, D., Kancharla, A., Nilsson, H., Vishnu, N., Mulder, H., Johansson, M., Rosselló, C. A., & Alvarado-Kristensson, M. (2018) · Communications Biology · doi:10.1038/s42003-018-0037-3 · Cited by 24
Fetal Cerebral Artery Mitochondrion as Target of Prenatal Alcohol Exposure
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“Moreover, modulation of these basic processes by cell signaling results in modifications of mitochondria shape and function [33,34].”
Background
Redox Regulation of the Mitochondrial Quality Control Protease Oma1
Bohovych, I., Dietz, J. V., Swenson, S. A., Zahayko, N., & Khalimonchuk, O. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7642 · Cited by 24
“The protease is largely dormant under normal physiological conditions, but it becomes rapidly activated by various stress stimuli such as loss of mitochondrial membrane potential, metabolic crisis, heat, and oxidative insults (11, 13, 16, 17, 20).”
Background
Salmonella enterica serovar Typhimurium remodels mitochondrial dynamics of macrophages via the T3SS effector SipA to promote intracellular proliferation
Liu, X., Liu, Y., Zhao, X., Li, X., Yao, T., Liu, R., Wang, Q., Wang, Q., Li, D., Chen, X., et al. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2316932 · Cited by 21
Ruthenium complex exerts antineoplastic effects that are mediated by oxidative stress without inducing toxicity in Walker-256 tumor-bearing rats
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Negatively Regulated by miR-29c-3p, MTFR1 Promotes the Progression and Glycolysis in Lung Adenocarcinoma via the AMPK/mTOR Signalling Pathway
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“Mitochondria are in constant dynamic equilibrium between fission and fusion to adapt to functional changes (Chan, 2006; Knott et al., 2008; Chan, 2012).”
Background
Cytological and proteomic evidence reveals the involvement of mitochondria in hypoxia-induced quality degradation in postharvest citrus fruit
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Alteration of Mitochondrial DNA Copy Number and Increased Expression Levels of Mitochondrial Dynamics-Related Genes in Sjögren’s Syndrome
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“While the reduction in mitochondrial fusion induces mitochondrion fragmentation, the reduction in mitochondrial fission leads to elongated and excessively interconnected mitochondrion [17].”
Background
Peripheral neuropathy in mitochondrial disease
Horváth, R., Medina, J. M., Reilly, M. M., Shy, M. E., & Zuchner, S. L. (2023) · Handbook of clinical neurology · doi:10.1016/b978-0-12-821751-1.00014-2 · Cited by 22
Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis
Chiu, F.-C., Kuo, H., Yu, C.-L., Selvam, P., Su, I.-L., Tseng, C., Yuan, C., & Wen, Z.-H. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.04.235 · Cited by 22
SS-31 treatment ameliorates cardiac mitochondrial morphology and defective mitophagy in a murine model of Barth syndrome
Russo, S., Rasmo, D. D., Rossi, R., Signorile, A., & Lobasso, S. (2024) · Scientific Reports · doi:10.1038/s41598-024-64368-y · Cited by 23
Mitochondrial 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
“Fragmentation of these mitochondrial networks through organelle ﬁssion and network regeneration via organelle fusion are necessary to distribute mitochondria to daughter cells during cell mitosis (5).”
MiR-106b-mediated Mfn2 suppression is critical for PKM2 induced mitochondrial fusion.
Wu, H., Li, Z., Wang, Y., Yang, P., Li, Z., Li, H., & Wu, C. (2016) · PubMed Central · Cited by 22
Atlastin regulates store-operated calcium entry for nerve growth factor-induced neurite outgrowth
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Antibiotics-Induced Obesity: A Mitochondrial Perspective
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Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus
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“In the majority of cells, including neuronal cells, mitochondria form a dynamic tubular network that is continuously remodeled; they may either divide via binary fission and form separate entities, or fuse and form a more continuous network (4).”
Background
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MitoTNT: Mitochondrial Temporal Network Tracking for 4D live-cell fluorescence microscopy data
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“Asymmetric fission/fusion events between large healthy mitochondria and small unhealthy mitochondria have been proposed to separate dysfunctional mitochondria targeted for mitophagy, or rescue damaged mitochondria by supplying essential materials [32,33].”
Background
Micropatterning Facilitates the Long‐Term Growth and Analysis of iPSC‐Derived Individual Human Neurons and Neuronal Networks
Burbulla, L. F., Beaumont, K. G., Mrksich, M., & Krainc, D. (2016) · Advanced Healthcare Materials · doi:10.1002/adhm.201500900 · Cited by 22
Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes
Jang, Y., Kim, J., Jeong, S., Paik, M.-K., Kim, J. S., & Cho, M. (2016) · The Journal of Toxicological Sciences · doi:10.2131/jts.41.731 · Cited by 21
“A central player in mitochondrial fission is DRP1, which is regulated by phosphorylation such as phosphorylation at Ser616 that activates fragmentation activity (Chan, 2012; Gomez-Lazaro et al., 2008).”
Three‐dimensional analysis of somatic mitochondrial dynamics in fission‐deficient injured motor neurons using FIB/SEM
Tamada, H., Kiryu‐Seo, S., Hosokawa, H., Ohta, K., Ishihara, N., Nomura, M., Mihara, K., Nakamura, K., & Kiyama, H. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24213 · Cited by 21
“Mitochondria can change their morphology by fission and fusion in response to changes of their intracellular and extracellular environments (Chan, 2012).”
Background
A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects
Delerue, T., Tribouillard‐Tanvier, D., Daloyau, M., Khosrobakhsh, F., Emorine, L. J., Friocourt, G., Belenguer, P., Blondel, M., & Pelloquin, L. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.036558 · Cited by 21
“…dynamics also underlies the adaptation of the organelle to energetic needs and ensures quality control through the complementation or destruction of damaged mitochondria, while directing cells towards apoptosis in cases of severe defects (Bertholet et al., 2016; Chan, 2012; Labbé et al., 2014).”
Rsp5 and Mdm30 reshape the mitochondrial network in response to age-induced vacuole stress
Goodrum, J. M., Lever, A. R., Coody, T. K., Gottschling, D. E., & Hughes, A. L. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-02-0094 · Cited by 23
“…control the levels and/or activity of key fusion and fission factors, including the fusion GTPases Opa1 and Mfn1/2 (yeast Mgm1 and Fzo1, respectively) and the fission GTPase Drp1 (yeast Dnm1; Chan, 2012; Youle and van der Bliek, 2012; Elgass et al. , 2013; Mishra and Chan, 2014; Roy et al. , 2015).”
Influential
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“a huge dynamic network, which increases their anti-stress ability as the mildly damaged mitochondria can be repaired by fusing with healthy ones, while the severely damaged parts of mitochondria can be segregated from the network by fission [13].”
Background
Cognitive dysfunction in chemobrain: Molecular mechanisms and therapeutic implications
Kim, H., Rashid, M. A., Poleschuk, M., Ullah, F., Lee, S., Kim, S., Qin, B., Zheng, X., & Jang, M.-H. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118581 · Cited by 25
“Mitochondrial dynamics, encompassing the processes of fission and fusion, are critical for maintaining mitochondrial quality control, distributing mitochondria within neurons, and supporting synaptic plasticity [29].”
Stochastic Models for Evolving Cellular Populations of Mitochondria: Disease, Development, and Ageing
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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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