Cited by 734Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

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Mitochondrial fusion and fission: The fine‐tune balance for cellular homeostasis

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Adebayo, Mary, Singh, Seema, Singh, Ajay Pratap, Dasgupta, Santanu·2021·The FASEB Journal

DOI 10.1096/fj.202100067rPMC PMC8415099

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Abstract

Mitochondria are highly dynamic, maternally inherited cytoplasmic organelles, which fulfill cellular energy demand through the oxidative phosphorylation system. Besides, they play an active role in calcium and damage‐associated molecular patterns signaling, amino acid, and lipid metabolism, and apoptosis. Thus, the maintenance of mitochondrial integrity and homeostasis is extremely critical, which is achieved through continual fusion and fission. Mitochondrial fusion allows the transfer of gene products between mitochondria for optimal functioning, especially under metabolic and environmental stress. On the other hand, fission is crucial for mitochondrial division and quality control. The imbalance between these two processes is associated with various ailments such as cancer, neurodegenerative and cardiovascular diseases. This review discusses the molecular mechanisms that control mitochondrial fusion and fission and how the disruption of mitochondrial dynamics manifests into various disease conditions.

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Background
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Background
Moderate replacement of fish oil with palmitic acid-stimulated mitochondrial fusion promotes β-oxidation by Mfn2 interacting with Cpt1α via its GTPase-domain
Song, Y., Wang, L., Luo, Z., Högstrand, C., Lai, X., & Zheng, F.-F. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2023.109559 · Cited by 18
ARMC10 regulates mitochondrial dynamics and affects mitochondrial function via the Wnt/β‐catenin signalling pathway involved in ischaemic stroke
Huang, Y., Zhang, Z., Xu, Y., Peng, Y., Xu, R., Luan, Y., Bie, X., Jia, J., Zhang, C., Han, T., et al. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18449 · Cited by 18
“30,31 ATP synthesis and ROS production are often used as important indicators for evaluating mitochondrial function.”
Background
The Role and Applied Value of Mitochondria in Glioma‐Related Research
Chen, L., Zhang, H., Shang, C., & Hong, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70121 · Cited by 18
“Mitochondrial fission is essential for mitochondrial division and quality control [68].”
Impaired endothelial function contributes to cardiac dysfunction: role of mitochondrial dynamics
Gutierrez‐Huerta, C. A., Quiroz-Delfi, G., Faleel, F. D. M., & Beyer, A. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00531.2024 · Cited by 18
Research progress on the role of mitochondria in the process of hepatic ischemia-reperfusion injury
Zhou, Y., Qiu, T., Wang, T., Yu, B., Xia, K., Guo, J., Liu, Y., Ma, X., Zhang, L., Zou, J., et al. (2023) · Gastroenterology report · doi:10.1093/gastro/goae066 · Cited by 19
Flaviviruses manipulate mitochondrial processes to evade the innate immune response
Boytz, R., Keita, K., Pawlak, J. B., & Laurent-Rolle, M. (2024) · npj Viruses · doi:10.1038/s44298-024-00057-x · Cited by 17
“Opa1 also helps maintain cristae structure and is involved in apoptosis regulation 19,21 .”
Background
Molecular mechanisms of mitochondrial homeostasis regulation in neurons and possible therapeutic approaches for Alzheimer's disease
Ren, J., Xiang, B., Xueling, L., Han, X., Yang, Z., Zhang, M., & Zhang, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e36470 · Cited by 16
“Mitochondrial fusion and fission are essential to mitochondrial homeostasis and energy adaptation [58].”
Background
Tetrahydrobenzimidazole TMQ0153 targets OPA1 and restores drug sensitivity in AML via ROS-induced mitochondrial metabolic reprogramming
Park, S. J., Cerella, C., Kang, J. M., Byun, J., Kum, D., Orlikova-Boyer, B., Lorant, A., Schnekenburger, M., Al‐Mourabit, A., Christov, C., et al. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03372-0 · Cited by 18
“Mitochondria are highly dynamic organelles in eukaryotic cells that continuously reshape their structure through fusion and fission [10], and are essential for cristae remodeling and cell survival [11].”
Mechanisms of endothelial senescence and vascular aging
Qiao, L., Qian, Z., Huang, Y., Yang, X. F., Yang, J., Xiao, N., Liang, G., Zhang, H., Fu, Y., Yan, L., et al. (2025) · Biogerontology · doi:10.1007/s10522-025-10279-y · Cited by 21
“Mild mitochondria damage can induce mitochondria fission or fusion to promote the elimination of damaged mitochondria segregation (Twig et al. 2008; Adebayo et al. 2021).”
Modulation of mitochondrial dysfunction: Mechanisms and strategies for the use of natural products to treat stroke
Qin, N., Liu, R., Deng, R., Shi, L., Wang, L., & Zhu, T. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00016 · Cited by 16
“Ligustilide (LIG), the primary active component in the traditional medicinal plants Ligusticum chuanxiong Hort ( Chuanxiong ) and Angelica sinensis , mitigates IS injury by enhancing mitochondrial function.”
Influential
Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications
Liao, X., Wang, Y., Zhang, Z., Qu, X., & Zhou, G. (2026) · Mediators of Inflammation · doi:10.1155/mi/3168669 · Cited by 24
Mitochondrial dynamics in pulmonary disease: Implications for the potential therapeutics
Li, H., Dai, X., Zhou, J.-F., Wang, Y., Zhang, S., Guo, J., Shen, L., Yan, H., & Jiang, H. (2024) · Journal of Cellular Physiology · doi:10.1002/jcp.31370 · Cited by 19
“Mitochondrial inner membrane fusion is most efficient when S ‐ OPA1 and L ‐ OPA1 are present together (Adebayo et al., 2021).”
Peroxiredoxin 2 regulates DAF-16/FOXO mediated mitochondrial remodelling in response to exercise that is disrupted in ageing
Qin, X., Li, P., Casas-Martinez, J. C., Miranda‐Vizuete, A., McDermott, E. A., Dockery, P., Goljanek‐Whysall, K., & McDonagh, B. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.102003 · Cited by 17
“Another critical mechanism for mitochondrial health is fusion, where individual mitochondria merge to form a singular, enlarged structure [10].”
Background
High temperature changes the structure and function of spotted seabass (Lateolabrax maculatus) tissues and causes ER stress and mitochondrial homeostasis imbalance in liver
Yang, X., Wang, L., Lu, K., Li, X., Song, K., & Zhang, C. (2025) · Aquaculture · doi:10.1016/j.aquaculture.2024.742107 · Cited by 16
Players in Mitochondrial Dynamics and Female Reproduction
Zou, W., Ji, D., Zhang, Z., Yang, L., & Cao, Y. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.717328 · Cited by 18
“Mutation in MFN2 affects this interaction, leading to impairment in axonal mitochondrial transport (Adebayo et al., 2021).”
Background
Effects of Long-Term Exposure to Copper on Mitochondria-Mediated Apoptosis in Pig Liver
Hu, Z., Liao, J., Zhang, K., Huang, K., Li, Q., Lei, C., Han, Q., Zhang, H., Guo, J., Hu, L., et al. (2022) · Biological Trace Element Research · doi:10.1007/s12011-022-03303-6 · Cited by 16
“Fission in mammals is coordinated by a cytosolic protein dynamin-related protein 1 (Drp1) that recruited to the mitochondria by its adaptors present on the OMM [55].”
BackgroundInfluential
Zeb1 sustains hematopoietic stem cell functions by suppressing mitofusin-2-mediated mitochondrial fusion
Zhang, K., Zhao, H., Sheng, Y., Chen, X., Xu, P., Wang, J., Ji, Z., He, Y., Gao, W., & Zhu, H. H. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05194-w · Cited by 15
“Conversely, mitochondrial-fission-proteins, including Drp1 and Fis1, divide larger mitochondria into smaller and round-shaped ones, promoting a fragmented mitochondrial network [14, 19].”
Background
Mycobacterial protein PE_PGRS30 induces macrophage apoptosis through prohibitin 2 mitochondrial function interference
Matsumura, K., Τακακι, S., & Kirikae, T. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1080369 · Cited by 15
“Mitochondria are dynamic organelles that undergo fusion and fission continuously (Adebayo et al., 2021).”
Background
The deubiquitinase OTUB1 governs lung cancer cell fitness by modulating proteostasis of OXPHOS proteins
Sheryazdanova, A., Amoêdo, N. D., Dufour, S., Impens, F., Rossignol, R., & Sablina, A. A. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166767 · Cited by 15
Mitophagy: A Bridge Linking HMGB1 and Parkinson’s Disease Using Adult Zebrafish as a Model Organism
Razali, K., Nasir, M. H. M., Kumar, J., & Mohamed, W. M. Y. (2023) · Brain Sciences · doi:10.3390/brainsci13071076 · Cited by 15
“The fragmentation process is critical in mitochondrial quality control to maintain mitochondrial fusion-fission homeostasis [42].”
Background
Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury
Andrianova, N. V., Brezgunova, A. A., Buyan, M. I., Makievskaya, C. I., Buyan, A., Cherkesova, K. S., Pevzner, I. B., Zorova, L. D., Zorov, D. B., Plotnikov, E. Y., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063155 · Cited by 15
Mitochondrial aberrations in systemic lupus erythematosus pathogenesis: Insights and therapeutic implications
Li, H., Zhou, L., Zhou, W., Zhang, X., Shang, J., Feng, X., Yu, L., Fan, J., Ren, J., Zhang, R., et al. (2024) · Rheumatology & autoimmunity · doi:10.1002/rai2.12119 · Cited by 15
Bacteria–organelle communication in physiology and disease
Lee, Y.-T., Şentürk, M., Guan, Y., & Wang, M. C. (2024) · The Journal of Cell Biology · doi:10.1083/jcb.202310134 · Cited by 15
Cellular senescence as a key player in chronic heart failure pathogenesis: Unraveling mechanisms and therapeutic opportunities
Zhao, S., Zhang, Y., Zhao, Y. R., & Lu, X. (2025) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2025.02.002 · Cited by 15
Mitochondrial bioenergetics and networks in melanoma: an update
Giannitti, G., Paganoni, A. J. J., Marchesi, S., Garavaglia, R., & Fontana, F. (2025) · APOPTOSIS · doi:10.1007/s10495-025-02155-4 · Cited by 15
“Mitochondrial shape, tightly controlled by the balance of fission and fusion, reflects and regulates metabolic activity and apoptosis [51].”
Mechanisms and therapeutic perspectives of mitochondrial dysfunction of macrophages in periodontitis
Jia, Y., Li, Z., Huang, P., Wang, Y., & Yang, B. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1634909 · Cited by 17
MFN2 and BAG6 Synergistically Protect Against Cerebral Reperfusion Injury by Regulating ROS Levels and Autophagic Flux
Lu, D., Yang, Y., Huang, G., Ye, Q., Quan, X., Kaltwasser, B., Liu, Y., Hermann, D. M., Brockmeier, U., & Wang, Y. (2025) · Stroke · doi:10.1161/strokeaha.125.052689 · Cited by 14
“41 However, polarized cells like neurons are highly sensitive to local energy shortages: Their energy demand is high at synaptic terminals and requires efficient microtubule-based axonal transport of smaller mitochondria.”
Oxidative Stress and Mitochondrial Dysfunction in Cardiovascular Aging: Current Insights and Therapeutic Advances
Azan, N. I. N., Karim, N. A., Sulaiman, N. S., Ng, M. H., Najib, A. M., Hassan, H., & Alias, E. (2026) · Biomedicines · doi:10.3390/biomedicines14010100 · Cited by 17
“They play a central role in mitochondrial inner membrane fusion and the maintenance of cristae structure [12,61,62].”
Influential
Fluoride-Induced Mitochondrial Dysfunction and Approaches for Its Intervention
Kumar, S., Shenoy, S., Swamy, R. S., Ravichandiran, V., & Kumar, N. (2023) · Biological Trace Element Research · doi:10.1007/s12011-023-03720-1 · Cited by 14
“Fluorosis can cause mitochondrial dysfunction by disrupting the balance between fission and fusion, leading to abnormal mitochondrial morphology [131].”
DRP1 knockdown and atorvastatin alleviate ox-LDL-induced vascular endothelial cells injury: DRP1 is a potential target for preventing atherosclerosis
Liu, S. Y., Zhao, Y., Yao, H., Zhang, L., Chen, C., Zheng, Z., & Jin, S. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113688 · Cited by 13
Enrofloxacin (ENR) exposure induces lipotoxicity by promoting mitochondrial fragmentation via dephosphorylation of DRP1 at S627 site
Wei, X., Xu, Y.-C., Tan, X.-Y., Lv, W.-H., Zhang, D.-G., He, Y., & Luo, Z. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2023.139892 · Cited by 16
ROLE OF MICROGLIA IN SEPSIS-ASSOCIATED ENCEPHALOPATHY PATHOGENESIS: AN UPDATE
Yu, Z., Shi, H., Zhang, J., Ma, C., He, C., Yang, F., & Zhao, L. (2023) · Shock · doi:10.1097/shk.0000000000002296 · Cited by 16
“Mitochondrial dysfunction can contribute to SAE through mechanisms such as an imbalance in the ratio of mitochondrial fusion/disintegration and impaired mitochondrial respiratory chain activity (95,96).”
Background
QiDongNing induces lung cancer cell apoptosis via triggering P53 / DRP1 ‐mediated mitochondrial fission
Ding, R., Wang, Y., Xu, L., Sang, S., Wu, G., Yang, W., Zhang, Y., Wang, C., Qi, A., Xie, H., et al. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18353 · Cited by 14
Imbalanced mitochondrial dynamics contributes to the pathogenesis of X-linked adrenoleukodystrophy
Launay, N., Lopez-Erauskin, J., Bianchi, P., Guha, S., Parameswaran, J., Coppa, A., Torreni, L., Schlüter, A., Fourcade, S., Paredes-Fuentes, A. J., et al. (2024) · Brain · doi:10.1093/brain/awae038 · Cited by 14
Venetoclax resistance in acute lymphoblastic leukemia is characterized by increased mitochondrial activity and can be overcome by co-targeting oxidative phosphorylation
Enzenmüller, S., Niedermayer, A., Seyfried, F., Muench, V., Tews, D., Rupp, U., Tausch, E., Groß, A., Fischer‐Posovszky, P., Walther, P., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06864-7 · Cited by 16
Regulation of mitochondrial dynamics in cardiomyocytes: implications for cardiac health and disease
Zhang, T., Li, Z., Xu, Y., Xu, C., Wang, H., & Tao, R. X. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1652683 · Cited by 17
Acetyl-CoA carboxylase 1 inhibition increases Treg metabolism and graft-versus-host disease treatment efficacy via mitochondrial fusion
McDonald-Hyman, C. S., Aguilar, E. G., Compeer, E. B., Zaiken, M. C., Rhee, S. Y., Mohamed, F. A., Larson, J. H., Loschi, M. L., Lees, C. J., Thangavelu, G., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci182480 · Cited by 14
“Mitochondria continuously undergo a dynamic process of fusion and fission, depending on cellular energy demands (51).”
Beyond energy: Mitochondrial control of platelet lifecycle through redox, calcium, and dynamics
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“Drp1 drives mitochondrial fission, whereas mitofusion-1 (Mfn1), Mfn2, and Optic atrophy-1 (Opa1) orchestrate OMM and IMM fusion, respectively [126,128].”
Mdivi-1 promotes lipid droplets-mitochondria contact and ameliorates cardiac lipotoxicity in high-fat diet-fed mice
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Authors: Adebayo, M., Singh, S., Singh, A. P., & Dasgupta, S.
Affiliations: USA Mitchell Cancer Institute (US)
Corresponding author: Singh, Ajay Pratap
Dasgupta, Santanu
ORCID: Singh, Seema
Dasgupta, Santanu
Venue: The FASEB Journal
Publisher: Wiley
Published: 2021-05-28
Volume: 35
Issue: 6
Pages: e21620-e21620
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.202100067r
PMC: PMC8415099
OpenAlex: W3164775823
Cited by: 733
References: 103
Citations by year: 2026: 189 · 2025: 235 · 2024: 183 · 2023: 83 · 2022: 38 · 2021: 4
FWCI: 8.11
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (CA185490, CA224306, CA204801, CA231925)
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 homeostasis, mitochondrial quality control, mitochondrial division, oxidative phosphorylation, calcium signaling, damage-associated molecular patterns, apoptosis, mitochondrial metabolism, neurodegenerative diseases, cardiovascular disease, cancer
MeSH terms: Animals, Homeostasis, Humans, Mitochondria, Mitochondrial Dynamics

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Mitochondrial fusion and fission: The fine‐tune balance for cellular homeostasis

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