The systems biology of mitochondrial fission and fusion and implications for disease and aging

Chauhan, Anuradha; Vera, Julio; Wolkenhauer, Olaf

doi:10.1007/s10522-013-9474-z

Cited by 52Mitochondrial Function and PathologyAutophagy in Disease and TherapyGenetics, Aging, and Longevity in Model Organisms

The systems biology of mitochondrial fission and fusion and implications for disease and aging

Chauhan, Anuradha, Vera, Julio, Wolkenhauer, Olaf·2014·Biogerontology

DOI 10.1007/s10522-013-9474-z

Open this paper in CoChat — free account

Abstract

Mitochondria organize themselves as dynamic populations within a cell, by undergoing continuous cycles of fission and fusion. The spatio-temporal distribution and abundance of mitochondria determines the cell’s energy budget and is thus intimately linked to the cell’s response to environmental stimuli during aging. The dynamic balance of mitochondrial fission and fusion can be studied in terms of antagonistic subpopulations that regulate the mitochondrial responses in space and time. The dynamic nature of these processes motivates mathematical modelling and the simulation of such complex process. In several neurodegenerative and metabolic diseases the dynamic balance of fission and fusion is disturbed. However, how this dynamics plays a role in the progression of diseases is largely unclear. Fission and fusion help mitochondria to regulate cellular energy (ATP) levels, and minimize accumulation of harmful oxidized material called reactive oxygen species which accelerate mutations in mitochondrial DNA (mtDNA) during aging. We discuss how systems biology approaches can be used to investigate the mechanisms controlling the fission–fusion dynamics under two categories: dissecting the design of its molecular regulatory motifs, and understanding complex mitochondrial responses through their population level interactions. This will help us to understand how different regulatory mechanisms regulate the ATP and mutation (mtDNA) landscape of mitochondria to a variety of environmental stimuli in order to maintain their function during aging.

Integrity signals

Registry

Crossref · 10.1007/s10522-013-9474-z

Cites

98 of 98 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Ageing is associated with decreases in both fission and fusion.
“As expected, ageing is associated with decreases in both fission and fusion (Bereiter-Hahn, 2014; Chauhan et al., 2014; Jendrach et al., 2005; Seo et al., 2010).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Chauhan et al., 2014

Simple model of spiking neurons
Izhikevich, E. M. (2003) · IEEE Transactions on Neural Networks · doi:10.1109/tnn.2003.820440 · Cited by 4,828 · see citing works
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674 · see citing works
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
Network motifs: theory and experimental approaches
Alon, U. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2102 · Cited by 3,279 · 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
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060 · see citing works
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734 · see citing works
Modeling and Simulation of Genetic Regulatory Systems: A Literature Review
de Jong, H. (2002) · Journal of Computational Biology · doi:10.1089/10665270252833208 · Cited by 2,660 · see citing works
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165 · see citing works
Mitochondrial fusion and fission in cell life and death
Westermann, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3013 · Cited by 2,002 · cited 8× · see citing works
“ATP consuming process (Westermann 2010).”
BackgroundInfluential
The Biologic Clock: The Mitochondria?
Harman, D. (1972) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1972.tb00787.x · Cited by 1,991 · see citing works
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
Chan, D. C. (2006) · Cell · doi:10.1016/j.cell.2006.06.010 · Cited by 1,987 · see citing works
Mitochondria: More Than Just a Powerhouse
McBride, H. M., Neuspiel, M., & Wasiak, S. (2006) · Current Biology · doi:10.1016/j.cub.2006.06.054 · Cited by 1,985 · see citing works
Understanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984 · see citing works
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 · see citing works
High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease
Bender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1769 · Cited by 1,570 · 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
“Fission increases variability by dividing mitochondria into uneven sized daughters, and fusion reduces this variability by intermixing the mitochondrial content (Chen et al. 2005; Mazzoni and Falcone 2011) (Fig.”
Background
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
Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission.
Taguchi, N., Ishihara, N., Jofuku, A., Oka, T., & Mihara, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607279200 · Cited by 1,226 · see citing works
Design principles of biochemical oscillators
Novák, B., & Tyson, J. J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2530 · Cited by 1,137 · see citing works
Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria
Cereghetti, G. M., Stangherlin, A., de Brito, O. M., Chang, C. R., Blackstone, C., Bernardi, P., & Scorrano, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808249105 · Cited by 1,129 · see citing works
Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability
Ferrell, J. E. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00314-9 · Cited by 1,121 · see citing works
Reversible phosphorylation of Drp1 by cyclic AMP‐dependent protein kinase and calcineurin regulates mitochondrial fission and cell death
Cribbs, J. T., & Strack, S. (2007) · EMBO Reports · doi:10.1038/sj.embor.7401062 · Cited by 1,024 · see citing works
Cellular Decision Making and Biological Noise: From Microbes to Mammals
Balázsi, G., van Oudenaarden, A., & Collins, J. J. (2011) · Cell · doi:10.1016/j.cell.2011.01.030 · Cited by 1,016 · see citing works
The chemical basis of morphogenesis
Turing, A. M. (1990) · Bulletin of Mathematical Biology · doi:10.1016/s0092-8240(05)80008-4 · Cited by 1,011 · see citing works
Bistability, Epigenetics, and Bet-Hedging in Bacteria
Veening, J., Smits, W. K., & Kuipers, O. P. (2008) · Annual Review of Microbiology · doi:10.1146/annurev.micro.62.081307.163002 · Cited by 1,006 · see citing works
The common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988 · see citing works
Defining Network Topologies that Can Achieve Biochemical Adaptation
Ma, W., Trusina, A., El-Samad, H., Lim, W. A., & Tang, C. (2009) · Cell · doi:10.1016/j.cell.2009.06.013 · Cited by 919 · see citing works
Regulation of mitochondrial morphology through proteolytic cleavage of OPA1
Ishihara, N., Fujita, Y., Oka, T., & Mihara, K. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601184 · Cited by 899 · see citing works
Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence
Passos, J. F., Saretzki, G., Ahmed, S., Nelson, G., Richter, T., Peters, H., Wappler, I., Birket, M. J., Harold, G., Schaeuble, K., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050110 · Cited by 796 · cited 2× · see citing works
“Since mitochondrial responses are linked to pathophysiological conditions, cell survival and aging (Cortassa et al. 2004; Passos et al. 2007; Aon et al. 2008; Shutt et al. 2012), it is an important challenge to understand how complex mitochondrial responses emerge.”
Background
Understanding Nonlinear Dynamics
Kaplan, D. T., Glass, L., & Berger, S. A. (1996) · Physics Today · doi:10.1063/1.2807512 · Cited by 678 · see citing works
Upregulated function of mitochondria‐associated ER membranes in Alzheimer disease
Area‐Gomez, E., del Carmen Lara Castillo, M., Tambini, M. D., Guardia‐Laguarta, C., de Groof, A. J. C., Madra, M., Ikenouchi, J., Umeda, M., Bird, T. D., Sturley, S. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.202 · Cited by 638 · see citing works
Taking a good look at free radicals in the aging process
Hekimi, S., Lapointe, J., & Wen, Y. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.06.008 · Cited by 606 · see citing works
Mitochondria are morphologically and functionally heterogeneous within cells
Collins, T. J., Berridge, M. J., Lipp, P., & Bootman, M. D. (2002) · The EMBO Journal · doi:10.1093/emboj/21.7.1616 · Cited by 588 · see citing works
Understanding Nonlinear Dynamics
Kaplan, D. T., & Glass, L. (1995) · Texts in applied mathematics · doi:10.1007/978-1-4612-0823-5 · Cited by 581 · see citing works
Dynamic regulation of mitochondrial fission through modification of the dynamin‐related protein Drp1
Chang, C., & Blackstone, C. D. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05629.x · Cited by 570 · see citing works
Mitochondrial mutations may increase oxidative stress: Implications for carcinogenesis and aging?
Bandy, B., & Davison, A. J. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90152-9 · Cited by 550 · 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 · cited 3× · see citing works
“Furthermore, aging reduces fission and fusion capacity (Jendrach et al. 2005; Seo et al. 2010).”
Background
Ca2+ transfer from the ER to mitochondria: When, how and why
Rizzuto, R., Marchi, S., Bonora, M., Aguiari, P., Bononi, A., Stefani, D. D., Giorgi, C., Leo, S., Rimessi, A., Siviero, R., et al. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.03.015 · Cited by 479 · see citing works
Spontaneous Synchronization of Coupled Circadian Oscillators
Gonze, D., Bernard, S., Waltermann, C., Kramer, A., & Herzel, H. (2005) · Biophysical Journal · doi:10.1529/biophysj.104.058388 · Cited by 465 · see citing works
The chemical basis of morphogenesis
Turing, A. M. (1990) · Bulletin of Mathematical Biology · doi:10.1007/bf02459572 · Cited by 434 · see citing works
Proteolytic Processing of OPA1 Links Mitochondrial Dysfunction to Alterations in Mitochondrial Morphology
Duvezin‐Caubet, S., Jagasia, R., Wagener, J., Hofmann, S., Trifunović, A., Hansson, A., Chomyn, A., Bauer, M. F., Attardi, G. M., Larsson, N., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606059200 · Cited by 431 · see citing works
Mitochondrial fission in apoptosis, neurodegeneration and aging
Bossy‐Wetzel, E., Barsoum, M. J., Godzik, A., Schwarzenbacher, R., & Lipton, S. A. (2003) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2003.10.015 · Cited by 428 · see citing works
Partial Differential Equations: An Introduction
Strauss, W. A. (1992) · Cited by 418 · see citing works
A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase.
Goldbeter, A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.20.9107 · Cited by 406 · see citing works
Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise
Cartoni, R., Léger, B., Hock, M. B., Praz, M., Crettenand, A., Pich, S., Ziltener, J., Luthi, F., Dériaz, O., Zorzano, A., et al. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.092031 · Cited by 406 · see citing works
Systems-Level Dissection of the Cell-Cycle Oscillator: Bypassing Positive Feedback Produces Damped Oscillations
Pomerening, J. R., Kim, S. Y., & Ferrell, J. E. (2005) · Cell · doi:10.1016/j.cell.2005.06.016 · Cited by 345 · see citing works
Mitochondrial ‘kiss‐and‐run’: interplay between mitochondrial motility and fusion–fission dynamics
Liu, X., Weaver, D., Shirihai, O. S., & Hajnóczky, G. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.255 · Cited by 344 · see citing works
Measuring and Modeling Apoptosis in Single Cells
Spencer, S. L., & Sorger, P. K. (2011) · Cell · doi:10.1016/j.cell.2011.03.002 · Cited by 333 · see citing works
The intracellular redox state is a core determinant of mitochondrial fusion
Shutt, T. E., Geoffrion, M., Milne, R. W., & McBride, H. M. (2012) · EMBO Reports · doi:10.1038/embor.2012.128 · Cited by 243 · see citing works
Mathematical Modeling Identifies Inhibitors of Apoptosis as Mediators of Positive Feedback and Bistability
Legewie, S., Blüthgen, N., & Herzel, H. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020120 · Cited by 238 · see citing works
A Mitochondrial Oscillator Dependent on Reactive Oxygen Species
Cortassa, S., Aon, M. A., Winslow, R. L., & O’Rourke, B. (2004) · Biophysical Journal · doi:10.1529/biophysj.104.041749 · Cited by 235 · see citing works
Deleterious mitochondrial DNA mutations accumulate in aging human tissues
Arnheim, N., & Cortopassi, G. A. (1992) · Mutation Research/DNAging · doi:10.1016/0921-8734(92)90020-p · Cited by 215 · see citing works
Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes
Zorzano, A., Liesa, M., & Palacín, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.02.004 · Cited by 209 · see citing works
An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cells
Miquel, J. (1991) · Archives of Gerontology and Geriatrics · doi:10.1016/0167-4943(91)90022-i · Cited by 197 · see citing works
Morpho-dynamic changes of mitochondria during ageing of human endothelial cells
Jendrach, M., Pohl, S., Vöth, M., Kowald, A., Hammerstein, P., & Bereiter‐Hahn, J. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.002 · Cited by 170 · see citing works
Frequency and Selectivity of Mitochondrial Fusion Are Key to Its Quality Maintenance Function
Mouli, P. K., Twig, G., & Shirihai, O. S. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2008.12.3959 · Cited by 157 · see citing works
Energy transfer in "parasitic" cancer metabolism: Mitochondria are the powerhouse and Achilles' heel of tumor cells
Martinez-Outschoorn, U. E., Pestell, R. G., Howell, A., Tykocinski, M. L., Nagajyothi, F., Machado, F. S., Tanowitz, H. B., Sotgia, F., & Lisanti, M. P. (2011) · Cell Cycle · doi:10.4161/cc.10.24.18487 · Cited by 157 · see citing works
Mitochondrial morphology—emerging role in bioenergetics
Galloway, C. A., Lee, H., & Yoon, Y. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.09.035 · Cited by 150 · see citing works
Mitochondrial Oscillations in Physiology and Pathophysiology
Aon, M. A., Cortassa, S. C., & O'Rourke, B. P. (2008) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-09794-7_8 · Cited by 147 · see citing works
Mitochondrial fission and fusion dynamics: the long and short of it
Berman, S. B., Pineda, F. J., & Hardwick, J. M. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.57 · Cited by 146 · see citing works
A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis
Pellegrini, L., & Scorrano, L. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402145 · Cited by 143 · see citing works
Accumulation of Defective Mitochondria through Delayed Degradation of Damaged Organelles and Its Possible Role in the Ageing of Post-mitotic and Dividing Cells
Kowald, A., & Kirkwood, T. B. L. (2000) · Journal of Theoretical Biology · doi:10.1006/jtbi.1999.1046 · Cited by 127 · see citing works
The Fundamental Organization of Cardiac Mitochondria as a Network of Coupled Oscillators
Aon, M. A., Cortassa, S. C., & O'Rourke, B. P. (2006) · Biophysical Journal · doi:10.1529/biophysj.106.087817 · Cited by 127 · see citing works
Evolution of the mitochondrial fusion–fission cycle and its role in aging
Kowald, A., & Kirkwood, T. B. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101604108 · Cited by 126 · see citing works
Biological switches and clocks
Tyson, J. J., Albert, R., Goldbeter, A., Ruoff, P., & Sible, J. C. (2008) · Journal of The Royal Society Interface · doi:10.1098/rsif.2008.0179.focus · Cited by 124 · see citing works
Control of Mitochondrial Morphology Through Differential Interactions of Mitochondrial Fusion and Fission Proteins
Huang, P., Galloway, C. A., & Yoon, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020655 · Cited by 124 · see citing works
Mitochondrial Variability as a Source of Extrinsic Cellular Noise
Johnston, I. G., Gaál, B., das Neves, R. P., Enver, T., Iborra, F. J., & Jones, N. S. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002416 · Cited by 116 · see citing works
Deceleration of Fusion–Fission Cycles Improves Mitochondrial Quality Control during Aging
Figge, M. T., Reichert, A. S., Meyer‐Hermann, M., & Osiewacz, H. D. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002576 · Cited by 112 · see citing works
The role of mitochondria in aging of skeletal muscle
Figueiredo, P. A., Mota, M. P., Appell, H. J., & Duarte, J. A. (2008) · Biogerontology · doi:10.1007/s10522-007-9121-7 · Cited by 109 · see citing works
Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters
Kurz, F. T., Aon, M. A., O'Rourke, B. P., & Armoundas, A. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007562107 · Cited by 97 · see citing works
The phosphorylation state of Drp1 determines cell fate
Jahani‐Asl, A., & Slack, R. S. (2007) · EMBO Reports · doi:10.1038/sj.embor.7401077 · Cited by 95 · see citing works
Models for the Generation and Interpretation of GradientsPreprint
Meinhardt, H. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001362 · Cited by 95 · see citing works
Emergence of the Mitochondrial Reticulum from Fission and Fusion Dynamics
Sukhorukov, V. M., Dikov, D., Reichert, A. S., & Meyer‐Hermann, M. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002745 · Cited by 82 · see citing works
Phenotypes and tolerances in the design space of biochemical systems
Savageau, M. A., Coelho, P. M. B. M., Fasani, R. A., Tolla, D. A., & Salvador, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809869106 · Cited by 81 · see citing works
Stochastic approaches in systems biology
Ullah, M., & Wolkenhauer, O. (2009) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.78 · Cited by 79 · see citing works
Self-citation
Mitochondrial Dynamics and Motility Inside Living Vascular Endothelial Cells: Role of Bioenergetics
Giedt, R. J., Pfeiffer, D. R., Anastasios Matzavinos, A., Kao, C., & Alevriadou, B. R. (2012) · Annals of Biomedical Engineering · doi:10.1007/s10439-012-0568-6 · Cited by 71 · see citing works
Glucose sensing in the pancreatic beta cell: a computational systems analysis
Fridlyand, L. E., & Philipson, L. H. (2010) · Theoretical Biology and Medical Modelling · doi:10.1186/1742-4682-7-15 · Cited by 54 · see citing works
Mitochondria unite to survive
Blackstone, C. D., & Chang, C. (2011) · Nature Cell Biology · doi:10.1038/ncb0511-521 · Cited by 53 · see citing works
Stochastic Approaches for Systems Biology
Ullah, M., & Wolkenhauer, O. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0478-1 · Cited by 53 · see citing works
Self-citation
Magnitude and control of mitochondrial sensitivity to ADP
Jeneson, J. A. L., Schmitz, J. P. J., van den Broek, N. M. A., van Riel, N. A. W., Hilbers, P. A. J., Nicolay, K., & Prompers, J. J. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00370.2009 · Cited by 52 · see citing works
Alternative pathways as mechanism for the negative effects associated with overexpression of superoxide dismutase
Kowald, A., Lehrach, H. R., & Klipp, E. (2005) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2005.06.034 · Cited by 51 · see citing works
Stochastic Drift in Mitochondrial DNA Point Mutations: A Novel Perspective Ex Silico
Poovathingal, S. K., Gruber, J., Halliwell, B. B., & Gunawan, R. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000572 · Cited by 47 · see citing works
Enhanced Depolarization‐Evoked Calcium Signal and Reduced [ATP]/[ADP] Ratio Are Unrelated Events Induced by Oxidative Stress in Synaptosomes
Tretter, L., Chinopoulos, C., & Ádám‐Vizi, V. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69062529.x · Cited by 42 · see citing works
The mitochondrial outer membrane protein hFis1 regulates mitochondrial morphology and fission through self-interaction
Serasinghe, M. N., & Yoon, Y. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.09.009 · Cited by 40 · see citing works
Mitochondrial function, mitochondrial DNA and ageing: a reappraisal
Passarino, G., Rose, G., & Bellizzi, D. (2010) · Biogerontology (Dordrecht) · doi:10.1007/s10522-010-9294-3 · Cited by 32 · see citing works
Qualitatively distinct phenotypes in the design space of biochemical systems
Savageau, M. A., & Fasani, R. A. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.10.073 · Cited by 30 · see citing works
Regulation of mammalian cell cycle progression in the regenerating liver
Chauhan, A., Lorenzen, S., Herzel, H., & Bernard, S. (2011) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2011.05.026 · Cited by 30 · see citing works
Self-citation
On Circuit Functionality in Boolean Networks
Comet, J., Noual, M., Richard, A., Aracena, J., Calzone, L., Jacques Demongeot, A., Kaufman, M., Naldi, A., Snoussi, E. H., & Thieffry, D. (2013) · Bulletin of Mathematical Biology · doi:10.1007/s11538-013-9829-2 · Cited by 30 · see citing works
Mitochondrial shaping cuts
Escobar‐Henriques, M., & Langer, T. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.03.009 · Cited by 25 · see citing works
Does mtDNA nucleoid organization impact aging?
Bogenhagen, D. F. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.12.002 · Cited by 23 · see citing works
Post‐tetanic hyperpolarization, sodium‐potassium‐activated adenosine triphosphatase and high energy phosphate levels in garfish olfactory nerve.
McDougal, D. B., & Osborn, L. A. (1976) · The Journal of Physiology · doi:10.1113/jphysiol.1976.sp011310 · Cited by 19 · see citing works
Overexpression of PGC-1β improves insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes
Gao, C., Guang-ling, L., Liu, S., Chen, X.-H., Ji, C., Zhang, C., Xia, Z., & Guo, X. (2011) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-0789-2 · Cited by 16 · see citing works
Autoregulation of Free Radicals via Uncoupling Protein Control in Pancreatic β-Cell Mitochondria
Heuett, W. J., & Periwal, V. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.10.012 · Cited by 15 · see citing works
Selective Adaptation in Networks of Heterogeneous Populations: Model, Simulation, and Experiment
Wallach, A., Eytan, D., Marom, S., & Meir, R. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0040029 · Cited by 13 · see citing works
The importance of mitochondrial fusion in aging
Mazzoni, C., & Falcone, C. (2011) · Cell Cycle · doi:10.4161/cc.10.21.18181 · Cited by 3 · see citing works
Getting together
McCarthy, N. J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3444 · Cited by 2 · see citing works
Getting together
McCarthy, N. J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3362 · Cited by 1 · see citing works

Flagged first, then by citations

Sorted by citations

Brain aging and neurodegeneration: from a mitochondrial point of view
Grimm, A., & Eckert, A. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14037 · Cited by 565 · see citing works
Neuronal Cells Rearrangement During Aging and Neurodegenerative Disease: Metabolism, Oxidative Stress and Organelles Dynamic
Castelli, V., Benedetti, E., Antonosante, A., Catanesi, M., Pitari, G., Ippoliti, R., Cimini, A., & d’Angelo, M. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00132 · Cited by 211 · see citing works
Modelling the molecular mechanisms of aging
Auley, M. T. M., Guimera, A. M., Hodgson, D., Mcdonald, N., Mooney, K. M., Morgan, A. E., & Proctor, C. J. (2017) · Bioscience Reports · doi:10.1042/bsr20160177 · Cited by 212 · see citing works
Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer’s disease
Grimm, A., Friedland, K., & Eckert, A. (2015) · Biogerontology · doi:10.1007/s10522-015-9618-4 · Cited by 182 · see citing works
Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases
DeBalsi, K. L., Hoff, K. E., & Copeland, W. C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.006 · Cited by 180 · see citing works
Linking mitochondrial dynamics, cristae remodeling and supercomplex formation: How mitochondrial structure can regulate bioenergetics
Baker, N., Patel, J., & Khacho, M. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.06.003 · Cited by 168 · see citing works
Cigarette smoke extract affects mitochondrial function in alveolar epithelial cells
Ballweg, K., Mutze, K., Königshoff, M., Eickelberg, O., & Meiners, S. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00180.2014 · Cited by 128 · see citing works
Mitochondrial Dynamic Dysfunction as a Main Triggering Factor for Inflammation Associated Chronic Non-Communicable Diseases
Geto, Z., Molla, M. D., Challa, F., Belay, Y., & Getahun, T. (2020) · Journal of Inflammation Research · doi:10.2147/jir.s232009 · Cited by 110 · see citing works
Evidence for a common biological pathway linking three Parkinson's disease‐causing genes: parkin, PINK1 and DJ‐1
van der Merwe, C., Dashti, Z. J. S., Christoffels, A. G., Loos, B., & Bardien, S. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12872 · Cited by 106 · see citing works
Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration
Alaimo, A., Liñares, G. G., Bujjamer, J. M., Gorojod, R. M., Alcon, S. P., Martínez, J. H., Baldessari, A., Grecco, H. E., & Kotler, M. L. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02409-6 · Cited by 97 · see citing works
Mitochondrial function and mitochondrial DNA maintenance with advancing age
Gaziev, A. I., Abdullaev, S., & Podlutsky, A. (2014) · Biogerontology · doi:10.1007/s10522-014-9515-2 · Cited by 77 · see citing works
Mitochondrial pathways in human health and aging
Bornstein, R., González, B., & Johnson, S. C. (2020) · Mitochondrion · doi:10.1016/j.mito.2020.07.007 · Cited by 70 · see citing works
Mitochondrial targeting as a novel therapy for stroke
Borlongan, C., Russo, E., Nguyen, H., Lippert, T., Tuazon, J. P., & Napoli, E. (2018) · Brain Circulation · doi:10.4103/bc.bc_14_18 · Cited by 67 · see citing works
Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment
Toledo, C., Andrade, D. C., Díaz, H. S., Inestrosa, N. C., & Rio, R. D. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01655-0 · Cited by 58 · see citing works
Cellular Metabolism and Aging
Catic, A. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.12.003 · Cited by 58 · see citing works
Toxoplasma gondii Infection Is Associated with Mitochondrial Dysfunction in-Vitro
Syn, G., Anderson, D. R., Blackwell, J. M., & Jamieson, S. E. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00512 · Cited by 52 · see citing works
CoQ10 and Mitochondrial Dysfunction in Alzheimer’s Disease
Fišar, Z., & Hroudová, J. (2024) · Antioxidants · doi:10.3390/antiox13020191 · Cited by 55 · see citing works
Extension of Drosophila Lifespan by Astragalus polysaccharide through a Mechanism Dependent on Antioxidant and Insulin/IGF-1 Signaling
Yang, F., Xiu, M., Yang, S., Li, X., Tuo, W., Su, Y., He, J., & Liu, Y. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/6686748 · Cited by 47 · see citing works
The glycine betaine role in neurodegenerative, cardiovascular, hepatic, and renal diseases: Insights into disease and dysfunction networks
Rosas‐Rodríguez, J. A., & Valenzuela-Soto, E. M. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119943 · Cited by 46 · see citing works
Cerebral Mitochondrial Function and Cognitive Performance during Aging: A Longitudinal Study in NMRI Mice
Reutzel, M., Grewal, R., Dilberger, B., Silaidos, C. V., Joppe, A., & Eckert, G. P. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/4060769 · Cited by 41 · see citing works
Antioxidative Effects of Chrysoeriol via Activation of the Nrf2 Signaling Pathway and Modulation of Mitochondrial Function
Kim, M. H., Kwon, S. Y., Woo, S.-Y., Seo, W. D., & Kim, D. Y. (2021) · Molecules · doi:10.3390/molecules26020313 · Cited by 40 · see citing works
Role of microRNAs in neurodegeneration induced by environmental neurotoxicants and aging
Singh, T., & Yadav, S. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101068 · Cited by 39 · see citing works
Aqueous Extract from Astragalus membranaceus Can Improve the Function Degradation and Delay Aging on Drosophila melanogaster Through Antioxidant Mechanism
Zhang, J., Qiao, Y., Li, D., Hao, S., Zhang, F., Zhang, X., Li, A., & Qin, X. (2022) · Rejuvenation Research · doi:10.1089/rej.2021.0081 · Cited by 36 · see citing works
Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming
Rastogi, A., Joshi, P. K., Contreras, E., & Gama, V. (2019) · Cell Stress · doi:10.15698/cst2019.06.189 · Cited by 34 · see citing works
Oxidative phosphorylation mediated pathogenesis of Parkinson's disease and its implication via Akt signaling
Ali, M. Z., & Dholaniya, P. S. (2022) · Neurochemistry International · doi:10.1016/j.neuint.2022.105344 · Cited by 33 · see citing works
T-cell-restricted intracellular antigen 1 facilitates mitochondrial fragmentation by enhancing the expression of mitochondrial fission factor
Tak, H., Eun, J. W., Kim, J., Park, S. J., Kim, C., Ji, E., Lee, H., Kang, H., Cho, D., Lee, K., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.90 · Cited by 31 · see citing works
Understanding the Role of Dysfunctional and Healthy Mitochondria in Stroke Pathology and Its Treatment
Nguyen, H., Zarriello, S., Rajani, M., Tuazon, J. P., Napoli, E., & Borlongan, C. V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072127 · Cited by 27 · see citing works
Dysregulation of mitochondrial complexes and dynamics by chronic cigarette smoke exposure Utilizing MitoQC reporter mice
Wang, Q., Unwalla, H. J., & Rahman, I. (2022) · Mitochondrion · doi:10.1016/j.mito.2022.01.003 · Cited by 28 · see citing works
The Role of Mitochondrial Quality Control in Anthracycline‐Induced Cardiotoxicity: From Bench to Bedside
Li, Y., Lin, R., Peng, X., Wang, X., Liu, X., Li, L., Bai, R., Wen, S., Ruan, Y., Chang, X., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3659278 · Cited by 28 · see citing works
Betaine enhances the cellular survival via mitochondrial fusion and fission factors, MFN2 and DRP1
Kim, M. J. (2018) · Animal Cells and Systems · doi:10.1080/19768354.2018.1512523 · Cited by 23 · see citing works
OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory
Bevan, R. J., Williams, P. A., Waters, C. T., Thirgood, R. A., Mui, A., Seto, S., Good, M. A., Morgan, J. E., Votruba, M., & Erchova, I. A. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa101 · Cited by 22 · see citing works
The interplay between mitochondrial functionality and genome integrity in the prevention of human neurologic diseases
D’Errico, M., Parlanti, E., Pascucci, B., Filomeni, G., Mastroberardino, P. G., & Dogliotti, E. (2021) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2021.108977 · Cited by 20 · see citing works
Mitochondrial Dysfunction as a Key Event during Aging: From Synaptic Failure to Memory Loss
Jara, C., Torres, A. K., Olesen, M. A., & Tapia‐Rojas, C. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88445 · Cited by 19 · see citing works
Distinct roles of UVRAG and EGFR signaling in skeletal muscle homeostasis
Kim, M. J., Febbraro, D., Farkona, S., Gillmore, T., Son, J. E., Regeenes, R., Chang, H. H., Pollock‐Tahiri, E., Yang, J., Park, Y. J., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101185 · Cited by 19 · see citing works
Non-Coding RNA-Dependent Regulation of Mitochondrial Dynamics in Cancer Pathophysiology
Cantafio, M. E. G., Torcasio, R., Viglietto, G., & Amodio, N. (2023) · Non-Coding RNA · doi:10.3390/ncrna9010016 · Cited by 18 · see citing works
Recent Advances in the Treatment of Genetic Forms of Parkinson’s Disease: Hype or Hope?
Cavallieri, F., Cury, R. G., Guimarães, T. G., Fioravanti, V., Grisanti, S., Rossi, J., Monfrini, E., Zedde, M., Fonzo, A. D., Valzania, F., et al. (2023) · Cells · doi:10.3390/cells12050764 · Cited by 18 · see citing works
Mitochondria research and neurodegenerative diseases: On the track to understanding the biological world of high complexity
Mendes, D., Peixoto, F., Oliveira, M. M., Andrade, P. B., & Videira, R. A. (2022) · Mitochondrion · doi:10.1016/j.mito.2022.05.001 · Cited by 18 · see citing works
Transcriptomic Study of Spermatogenesis in the Testis of Hu Sheep and Tibetan Sheep
Fu, X., Yang, Y., Yan, Z., Liu, M., & Wang, X. (2022) · Genes · doi:10.3390/genes13122212 · Cited by 17 · see citing works
Mitochondria: fundamental characteristics, challenges, and impact on aging
Liang, R., Zhu, L., Huang, Y., Chen, J., & Tang, Q. (2024) · Biogerontology · doi:10.1007/s10522-024-10132-8 · Cited by 16 · see citing works
Age-related Mitochondrial Dysfunction in Parkinson's Disease: New Insights Into the Disease Pathology
Rani, L., Sahu, M. R., & Mondal, A. C. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.07.007 · Cited by 16 · see citing works
Population Dynamics of Mitochondria in Cells: A Minimal Mathematical Model
Kornick, K., Bogner, B. M., Sutter, L., & Das, M. (2019) · Frontiers in Physics · doi:10.3389/fphy.2019.00146 · Cited by 14 · see citing works
Mitochondrial dynamics in neurodegeneration: from cell death to energetic states
Khacho, M., & Slack, R. S. (2015) · AIMS molecular science · doi:10.3934/molsci.2015.2.161 · Cited by 13 · see citing works
Systems Biology Approaches in Aging Research
Chauhan, A., Liebal, U. W., Vera, J., Baltrusch, S., Junghanß, C., Tiedge, M., Fuellen, G., Olaf Wolkenhauer, A., & Köhling, R. (2014) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000364981 · Cited by 9 · see citing works
Self-citation
The role of mitochondrial DNA variants and dysfunction in the pathogenesis and progression of multiple sclerosis
Darehbagh, R. R., Khanmohammadi, S., & Rezaei, N. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.102002 · Cited by 5 · see citing works
Examining Mitochondrial Morphology in Mouse Brains
Royea, J., & Khacho, M. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2409-8_2 · Cited by 4 · see citing works
Mitochondria and Brain Disorders
Baloyannis, S. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.77668 · Cited by 4 · see citing works
Dual-targeted Mitophagy activation by curcumin-Zn co-delivery mediates neuroprotection in zebrafish through coordinated PINK1/Parkin and PI3K/AKT/mTOR pathway regulation
Pan, X., Li, Q., Yuan, D., Zhao, M., Gu, Z., & Zhou, F. (2025) · Food Research International · doi:10.1016/j.foodres.2025.117464 · Cited by 3 · see citing works
Understanding mitochondria and the utility of optimization as a canonical framework for identifying and modeling mitochondrial pathways
Benaroya, H. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2021-0138 · Cited by 1 · see citing works
Redox regulation in pulmonary fibrosis
Veith (2019) · doi:10.26481/dis.20190524cv · Cited by 1 · see citing works
Mitochondria as a Key Player in Aging
Banerjee, R., & Rath, P. C. (2020) · Springer eBooks · doi:10.1007/978-981-32-9005-1_10
Optimization in Mitochondrial Energetic Pathways
Benaroya, H. (2021) · doi:10.1002/9781119831839.ch1
Spermidine deficiency induces BNIP3/LC3B-mediated mitophagy in the salivary glands of accelerated aging mice
Toan, N. K., Duong, M. D., Phu, N. D., Thanh, L. V., & Ahn, S. (2025) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2025.130897

Mitochondrial fission and fusion: A dynamic role in aging and potential target for age-related disease
Liu, Y. J., McIntyre, R. L., Janssens, G. E., & Houtkooper, R. H. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111212 · Cited by 334 · see citing works
Bioenergetic role of mitochondrial fusion and fission
Westermann, B. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.02.033 · Cited by 687 · see citing works
Interplay of mitochondrial fission-fusion with cell cycle regulation: Possible impacts on stem cell and organismal aging
Spurlock, B., Tullet, J. M. A., Hartman, J. L., & Mitra, K. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110919 · Cited by 59 · see citing works
The evolution and role of mitochondrial fusion and fission in aging and disease
Kowald, A., & Kirkwood, T. B. L. (2011) · Communicative & Integrative Biology · doi:10.4161/cib.17110 · Cited by 17 · see citing works
Bioenergetic role of mitochondrial fusion and fission Bioenergetics
Westermann, B. (2012) · Biochimica et Biophysica Acta

Authors: Chauhan, A., Vera, J., & Wolkenhauer, O.
Affiliations: University of Rostock (DE)
Corresponding author: Chauhan, Anuradha
ORCID: Vera, Julio
Venue: Biogerontology
Publisher: Springer Science and Business Media LLC
Published: 2013-10-12
Volume: 15
Issue: 1
Pages: 1-12
ISSN: 1389-5729 (ISSN-L)
1573-6768
DOI: 10.1007/s10522-013-9474-z
OpenAlex: W2019617490
Cited by: 52
References: 98
Citations by year: 2025: 2 · 2024: 3 · 2023: 2 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 9 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 3
FWCI: 0.25
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Biogerontology (publishedVersion)
PubMed (publishedVersion)
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 › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: mitochondrial fission, mitochondrial fusion, mitochondrial dynamics, aging, neurodegenerative diseases, metabolic disorders, ATP production, reactive oxygen species, mitochondrial DNA mutations, systems biology
MeSH terms: Adaptation, Physiological, Aging, Animals, Disease, DNA, Mitochondrial, Energy Metabolism, Humans, Systems Biology, Cellular Microenvironment, Mitochondrial Dynamics

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

The systems biology of mitochondrial fission and fusion and implications for disease and aging

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks