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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Background
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Background
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Background
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Background
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Background
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Background
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BackgroundInfluential
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Background
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Background
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Background
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Background
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Background
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Background
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“Mitochondria are organelles characterized by structural and molecular dynamics undergoing fusion and division (202).”
Background
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Silver Nanoparticle Exposure Causes Pulmonary Structural Damage and Mitochondrial Dynamic Imbalance in the Rat: Protective Effects of Sodium Selenite
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“Drp1 plays a central role in fission, or at least the best understood fission protein, that regulates mitochondrial fission in mammals together with mitochondrial fission protein 1 (Fis1).(12,13) Mitochondrial fusion is a process where two mitochondria merged into one.”
Background
Plant sterol ester of α-linolenic acid ameliorates high-fat diet-induced nonalcoholic fatty liver disease in mice: association with regulating mitochondrial dysfunction and oxidative stress via activating AMPK signaling
Han, H., Li, X., Guo, Y., Zheng, M., Xue, T., & Wang, L. (2021) · Food & Function · doi:10.1039/d0fo02623a · Cited by 43
Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca2+ regulation in airway smooth muscle (ASM)
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“The balance between fission and fusion is now thought to be important for mitochondrial DNA stability, respiratory function, cell fate determination, and adaptation to cellular stress (Chan 2012).”
Background
Persistent Mitochondrial Hyperfusion Promotes G2/M Accumulation and Caspase-Dependent Cell Death
Westrate, L. M., Sayfie, A. D., Burgenske, D. M., & MacKeigan, J. P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091911 · Cited by 44
“Mitochondria play critical roles in meeting the bioenergetics needs of the cell, which include the generation of cellular ATP through oxidative phosphorylation [1].”
BackgroundInfluential
Inadequate mito-biogenesis in primary dermal fibroblasts from old humans is associated with impairment of PGC1A-independent stimulation
Kalfalah, F. M., Sobek, S., Bornholz, B., Götz-Rösch, C., Tigges, J., Fritsche, E., Krutmann, J., Köhrer, K., Deenen, R., Ohse, S., et al. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.017 · Cited by 45
“ageing-related modulations (Chan 2012; Figge and others 2012; Koziel and others 2011; Lemasters 2005).”
Background
Chemical genetics unveils a key role of mitochondrial dynamics, cytochrome c release and IP3R activity in muscular dystrophy
Giacomotto, J., Brouilly, N., Walter, L., Mariol, M., Berger, J., Ségalat, L., Becker, T. S., Currie, P. D., & Gieseler, K. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt302 · Cited by 45
“Mitochondria are dynamic organelles whose morphology and function are controlled by a balance between fission and fusion events (11).”
Background
PERK-Mediated Unfolded Protein Response Activation and Oxidative Stress in PARK20 Fibroblasts
Amodio, G., Moltedo, O., Fasano, D., Zerillo, L., Oliveti, M., Pietro, P. D., Faraonio, R., Barone, P., Pellecchia, M. T., Rosa, A. D., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00673 · Cited by 48
“Because mitochondrial function is linked to the overall organization of the mitochondrial network (Chan, 2012), we examined the mitochondrial morphology by using the Mitotracker Red CMXRos probe (Figure 6).”
Mitochondria: A worthwhile object for ultrastructural qualitative characterization and quantification of cells at physiological and pathophysiological states using conventional transmission electron microscopy
Ďúranová, H., Válková, V., Kňažická, Z., Olexíková, L., & Vašíček, J. (2020) · Acta Histochemica · doi:10.1016/j.acthis.2020.151646 · Cited by 47
The Interaction of Diet and Mitochondrial Dysfunction in Aging and Cognition
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Dietary Fucoxanthin Increases Metabolic Rate and Upregulated mRNA Expressions of the PGC-1alpha Network, Mitochondrial Biogenesis and Fusion Genes in White Adipose Tissues of Mice
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“Mitochondrial biogenesis and dynamics regulate mitochondrial function, respiratory capacity, apoptosis and oxidative phosphorylation and, thus, impact energy balance [3,12,36].”
Background
LONP1 downregulation with ageing contributes to osteoarthritis via mitochondrial dysfunction
He, Y., Ding, Q., Chen, W., Lin, C., Ge, L., Ying, C., Xu, K., Wu, Z., Xu, L., Ran, J., et al. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.08.038 · Cited by 43
The Potential of Mitochondrial Therapeutics in the Treatment of Oxidative Stress and Inflammation in Aging
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“As presently understood, normal mitochondrial function relies on a balance of fission and fusion processes, which allow mitochondria to adapt to changing cellular conditions and ensure mitochondrial quality by removing damaged mitochondria (mitophagy) [29].”
Influential
Mitochondrial mechanisms in Treg cell regulation: Implications for immunotherapy and disease treatment
Zhao, X., Zhang, J., Li, C., Kuang, W., Deng, J., Tan, X., Li, C., & Li, S. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101975 · Cited by 47
Mi RNA ‐30a inhibits AEC s‐II apoptosis by blocking mitochondrial fission dependent on Drp‐1
Mao, C., Zhang, J., Lin, S., Jing, L., Xiang, J., Wang, M., Wang, B., Xu, P., Liu, W., Song, X., et al. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12420 · Cited by 42
“Drp-1 is recruited from the cytoplasm to the mitochondria when excessive mitochondrial fission occurs [11, 12]; but, whether Drp-1 translocation is involved in the process of AECs-II mitochondrial fission remains ambiguous.”
Background
Can endurance exercise preconditioning prevention disuse muscle atrophy?
Wiggs, M. P. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00063 · Cited by 46
“…in Physiology | www.frontiersin.org 6 March 2015 | Volume 6 | Article 63 Dynamin-related protein-1 (Drp1) and Fission 1 (Fis1), whereas proteins regulating mitochondrial fusion include optic atrophy 1 (Opa1) and mitofusion 1 and 2 (Mfn1/2) (reviewed in Westermann, 2010; Chan, 2012).”
Background
The A rabidopsis mitochondrial membrane‐bound ubiquitin protease UBP 27 contributes to mitochondrial morphogenesis
Pan, R., Kaur, N., & Hu, J. (2014) · The Plant Journal · doi:10.1111/tpj.12532 · Cited by 42
The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity
Chaudhari, S. N., & Kipreos, E. T. (2018) · BioEssays · doi:10.1002/bies.201800005 · Cited by 42
Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma.
Qin, W., Wu, X.-D., Jia, Y., Tong, X., Guo, C., Chen, D., Wang, Z., & Tan, N. (2019) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2019.109188 · Cited by 37
Mitochondrial regulation in spermatogenesis
Zhang, Z., Miao, J., & Wang, Y. (2022) · Reproduction · doi:10.1530/rep-21-0431 · Cited by 41
“Mitochondrial dynamics and spermatogenesis Mitochondria are highly dynamic organelles, undergoing coordinated cycles of fission and fusion (Bereiter-Hahn & Voth 1994, Chan 2012).”
Background
Silica nanoparticles perturbed mitochondrial dynamics and induced myocardial apoptosis via PKA-DRP1-mitochondrial fission signaling
Zhao, X., Xu, H., Li, Y., Liu, Y., Li, X., Zhou, W. J., Wang, J., Guo, C., Sun, Z., & Li, Y. (2022) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2022.156854 · Cited by 41
Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction
Wang, F., Yang, J., Sun, J., Dong, Y., Zhao, H., Shi, H., & Fu, L. (2015) · Journal of Endocrinology · doi:10.1530/joe-14-0638 · Cited by 41
“…DOI: 10.1530/JOE-14-0638 Printed in Great Britain requires MFN2, and proper fission events, which require DRP1, are essential for mitochondrial integrity, respiratory capacity, oxidative phosphorylation, apoptosis, response to cellular stress, and mitophagy (Garnier et al. 2005, Chan 2012).”
BackgroundInfluential
A Comprehensive Review of Pathological Mechanisms and Natural Dietary Ingredients for the Management and Prevention of Sarcopenia
Kim, J., Lee, J.-Y., & Kim, C. Y. (2023) · Nutrients · doi:10.3390/nu15112625 · Cited by 45
“Satellite cells (SCs), skeletal muscle stem cells, regenerate repeatedly throughout life and preserve skeletal muscle integrity contributing to muscle mass and muscle regeneration after injury.”
Background
Distribution of mitochondrial nucleoids upon mitochondrial network fragmentation and network reintegration in HEPG2 cells
Tauber, J. A., Dlasková, A., Šantorová, J., Smolková, K., Alán, L., Špaček, T., Plecitá‐Hlavatá, L., Jabůrek, M., & Ježek, P. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.11.019 · Cited by 44
Distinct types of protease systems are involved in homeostasis regulation of mitochondrial morphology via balanced fusion and fission
Saita, S., Ishihara, T., Maeda, M., Iemura, S., Natsume, T., Mihara, K., & Ishihara, N. (2016) · Genes to Cells · doi:10.1111/gtc.12351 · Cited by 43
“Mitochondria are dynamic organelles that continually undergo frequent fusion and fission in response to the cell environment or cellular differentiation (Okamoto & Shaw 2005; McBride et al. 2006; Westermann 2010; Chan 2012).”
Background
Metabolism of Preimplantation Embryo Development
Kaneko, K. J. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2016.04.010 · Cited by 48
Adrenergic Regulation of Drp1-Driven Mitochondrial Fission in Cardiac Physio-Pathology
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Discovery of 6-Phenylhexanamide Derivatives as Potent Stereoselective Mitofusin Activators for the Treatment of Mitochondrial Diseases
Dang, X., Zhang, L., Franco, A., Li, J., Rocha, A. G., Devanathan, S., Dolle, R. E., Bernstein, P. R., & Dorn, G. W. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00366 · Cited by 42
The Complex Interplay between Imbalanced Mitochondrial Dynamics and Metabolic Disorders in Type 2 Diabetes
Huynh, T. V., Rethi, L., Rethi, L., Chen, C., Chen, Y., & Kao, Y. (2023) · Cells · doi:10.3390/cells12091223 · Cited by 42
Role of mitochondria in inflammatory lung diseases
Narala, V. R., Narala, S. R., Subramani, P. A., Panati, K., & Kolliputi, N. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1433961 · Cited by 43
“Fission is a process of vital importance to the cell, allowing for removal of damaged mitochondria and isolation of damaged portions of mitochondria to prevent spread of detrimental products to unaffected mitochondria (Chan, 2012).”
Background
TRIM4; a novel mitochondrial interacting RING E3 ligase, sensitizes the cells to hydrogen peroxide (H2O2) induced cell death
Tomar, D., Prajapati, P., Lavie, J., Singh, K., Sripada, L., Bhatelia, K., Roy, M., Singh, R. K., Bénard, G., & Singh, R. K. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.10.425 · Cited by 39
“Mitochondria are dynamic organelle that undergo the process of fusion and fission to adapt different stress conditions [43].”
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Form follows function for mitochondria
Wang, C., & Youle, R. J. (2016) · Nature · doi:10.1038/530288a · Cited by 42
Increased obesity resistance and insulin sensitivity in mice lacking the isocitrate dehydrogenase 2 gene
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Dysfunctional mitochondrial fission impairs cell reprogramming
Prieto, J., León, M., Ponsoda, X., Garcia‐García, F., Bort, R., Serna, E., Barneo‐Muñoz, M., Palau, F., Dopazo, J., López‐García, C., et al. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1241930 · Cited by 41
“mitochondrial membrane, forming a ring that eventually fragments mitochondria in a GTPase-dependent manner.(2,6)”
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Mechanotransduction and Metabolism in Cardiomyocyte Microdomains
Pasqualini, F. S., Nesmith, A. P., Horton, R. E., Sheehy, S. P., & Parker, K. K. (2016) · BioMed Research International · doi:10.1155/2016/4081638 · Cited by 41
“To achieve the number and spatial distribution observed in adult cells and to limit the degradation of their DNA, mitochondria continuously merge together (fusion) and split apart (fission) in a process termed mitochondrial biogenesis [40].”
Control of mitochondrial homeostasis by endocytic regulatory proteins
Farmer, T., Reinecke, J. B., Xie, S., Bahl, K., Naslavsky, N., & Caplan, S. (2017) · Journal of Cell Science · doi:10.1242/jcs.204537 · Cited by 43
“Mitochondrial function is closely controlled by their dynamics, and they are continually undergoing cycles of fusion and fission, processes required for homeostasis and mitochondrial health (Chan, 2012).”
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Mitochondrial biogenesis: a potential therapeutic target for osteoarthritis
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Targeted Antioxidants in Exercise-Induced Mitochondrial Oxidative Stress: Emphasis on DNA Damage
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“Mitochondria are recognised as multifaceted arbiters of the life and death of the cell, contributing to numerous cell networks including metabolism and biosynthetic pathways [1,2].”
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Knockdown of Mtfp1 can minimize doxorubicin cardiotoxicity by inhibiting Dnm1l‐mediated mitochondrial fission
Aung, L. H. H., Li, R., Prabhakar, B. S., & Li, P. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13250 · Cited by 44
FGF19 increases mitochondrial biogenesis and fusion in chondrocytes via the AMPKα-p38/MAPK pathway
Kan, S., Pi, C., Zhang, L., Guo, D., Niu, Z., Liu, Y., Duan, M., Pu, X., Bai, M., Zhou, C., et al. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01069-5 · Cited by 41
Integrating mitochondrial organization and dynamics with cellular architecture
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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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