{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:55:56Z","timestamp":1790758556658,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Defects in mitochondrial dynamics, fission, fusion, and motility have been implicated in the pathogenesis of multiple neurodegenerative diseases, including Parkinson\u2019s disease, Alzheimer\u2019s disease, Huntington\u2019s disease, and Charcot\u2013Marie\u2013Tooth disease. Another key feature of neurodegeneration is the increase in reactive oxygen species (ROS). Previous work has shown that the cytoskeleton, in particular the microtubules, and ROS generated by rotenone significantly regulate mitochondrial dynamics in Dictyostelium discoideum. The goal of this project is to study the effects of ROS on mitochondrial dynamics within our model organism D. discoideum to further understand the underlying issues that are the root of neurodegenerative diseases such as Alzheimer\u2019s disease and Parkinson\u2019s disease. We chose three likely ROS inducers, cumene hydroperoxide, hydroxylamine hydrochloride, and Antimycin A. Our work demonstrates that alteration of the microtubule cytoskeleton is not required to alter dynamics in response to ROS and there is no easy way to predict how mitochondrial dynamics will be altered based on which ROS generator is used. This research contributes to the better understanding of the cellular mechanisms that induce the pathogenesis of incurable neurodegenerative diseases with the hope that it will translate into developing new and more effective treatments for patients afflicted by them.<\/jats:p>","DOI":"10.3390\/cells10082147","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T08:44:45Z","timestamp":1629449085000},"page":"2147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identifying the Effects of Reactive Oxygen Species on Mitochondrial Dynamics and Cytoskeleton Stability in Dictyostelium discoideum"],"prefix":"10.3390","volume":"10","author":[{"given":"Evan","family":"Downs","sequence":"first","affiliation":[{"name":"Department of Biology, University of Central Arkansas, Conway, AR 72035, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber D.","family":"Bottrell","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Central Arkansas, Conway, AR 72035, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3222-1540","authenticated-orcid":false,"given":"Kari","family":"Naylor","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Central Arkansas, Conway, AR 72035, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41531-018-0058-0","article-title":"Prevalence of Parkinson\u2019s disease across North America","volume":"4","author":"Marras","year":"2018","journal-title":"Npj Parkinsons Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.tcb.2009.11.002","article-title":"Control of mitochondrial transport and localization in neurons","volume":"20","author":"MacAskill","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.tcb.2012.10.006","article-title":"Mitochondrial dynamics in neurodegeneration","volume":"23","author":"Itoh","year":"2013","journal-title":"Trends Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"R169","DOI":"10.1093\/hmg\/ddp326","article-title":"Mitochondrial dynamics\u2014Fusion, fission, movement, and mitophagy\u2014In neurodegenerative diseases","volume":"18","author":"Chen","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1056\/NEJMra1215233","article-title":"Mitochondrial dynamics\u2014Mitochondrial fission and fusion in human diseases","volume":"369","author":"Archer","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_6","first-page":"4033","article-title":"Structural and biomechanical basis of mitochondrial movement in eukaryotic cells","volume":"8","author":"Wu","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: In Sickness and in Health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Schimmel, B., Berbusse, G., and Naylor, K. (2012). Mitochondrial fission and fusion in Dictyostelium discoideum: A search for proteins involved in membrane dynamics. BMC Res. Notes, 5.","DOI":"10.1186\/1756-0500-5-505"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fcell.2016.00019","article-title":"Microtubules Are Essential for Mitochondrial Dynamics\u2014Fission, Fusion, and Motility\u2014In Dictyostelium discoideum","volume":"4","author":"Woods","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chernivec, E., Cooper, J., and Naylor, K. (2018). Exploring the Effect of Rotenone\u2014A Known Inducer of Parkinson\u2019s Disease\u2014On Mitochondrial Dynamics in Dictyostelium discoideum. Cells, 7.","DOI":"10.3390\/cells7110201"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11010-009-0111-8","article-title":"Dictyostelium discoideum\u2014A model for many reasons","volume":"329","author":"Annesley","year":"2009","journal-title":"Mol. Cell. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.semcdb.2010.11.004","article-title":"The Dictyostelium model for mitochondrial disease","volume":"22","author":"Francione","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1387\/ijdb.190233pf","article-title":"The Dictyostelium model for mitochondrial biology and disease","volume":"63","author":"Pearce","year":"2019","journal-title":"Int. J. Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1091\/mbc.8.7.1233","article-title":"Mitochondrial transmission during mating in S. cerevisiae is determined by mitochondrial fusion and fission and the intramitochondrial segregation of mtDNA","volume":"8","author":"Nunnari","year":"1997","journal-title":"Mol. Biol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1126\/science.1219855","article-title":"Mitochondrial Fission, Fusion, and Stress","volume":"337","author":"Youle","year":"2012","journal-title":"Science"},{"key":"ref_17","first-page":"9163040","article-title":"The Sources of Reactive Oxygen Species and Its Possible Role in the Pathogenesis of Parkinson\u2019s Disease","volume":"2018","author":"Weng","year":"2018","journal-title":"Parkinson\u2019s Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1046\/j.0022-3042.2002.00744.x","article-title":"Generation of reactive oxygen species by the mitochondrial electron transport chain","volume":"80","author":"Liu","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.bbabio.2012.12.002","article-title":"Superoxide generation by complex III: From mechanistic rationales to functional consequences","volume":"1827","author":"Bleier","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"607392","DOI":"10.3389\/fcell.2020.607392","article-title":"When Friendship Turns Sour: Effective Communication Between Mitochondria and Intracellular Organelles in Parkinson\u2019s Disease","volume":"8","author":"Lin","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_21","unstructured":"Berbusse, G. (2014). Investigating the Importance of Mitochondrial Dynamics: Fission, Fusion, Trafficking and Fragmentation in the Single-Celled Organism Dictyostelium discoideum and CD-1 Mice In Vitro. [Master\u2019s Thesis, University of Central Arkansas]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10863-006-9011-8","article-title":"Testing the vicious cycle theory of mitochondrial ROS production: Effects of H2O2 and cumene hydroperoxide treatment on heart mitochondria","volume":"38","author":"Sanz","year":"2006","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/jbt.20377","article-title":"Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors","volume":"25","author":"Vimard","year":"2011","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13646","DOI":"10.1016\/S0021-9258(17)43964-0","article-title":"Inhibition and reactivation of Mn-catalase. Implications for valence changes at the active site manganese","volume":"258","author":"Kono","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.1111\/j.1742-4658.2007.06083.x","article-title":"Effect of oxidative stress and involvement of poly(ADP-ribose) polymerase (PARP) in Dictyostelium discoideum development","volume":"274","author":"Rajawat","year":"2007","journal-title":"FEBS J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"813","DOI":"10.3892\/ijo.2015.3276","article-title":"Antimycin A induces death of the human pulmonary fibroblast cells via ROS increase and GSH depletion","volume":"48","author":"Park","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kim, J., and Cheong, J.H. (2020). Role of Mitochondria-Cytoskeleton Interactions in the Regulation of Mitochondrial Structure and Function in Cancer Stem Cells. Cells, 9.","DOI":"10.3390\/cells9071691"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cell.2005.02.001","article-title":"Mitochondria, oxidants, and aging","volume":"120","author":"Balaban","year":"2005","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8123","DOI":"10.1016\/S0021-9258(18)42415-5","article-title":"The effect of antimycin A on mouse liver inner mitochondrial membrane channel activity","volume":"267","author":"Campo","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of mitochondrial ROS in the brain: From physiology to neurodegeneration","volume":"592","author":"Angelova","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"428010","DOI":"10.1155\/2012\/428010","article-title":"Mechanism of Oxidative Stress in Neurodegeneration","volume":"2012","author":"Gandhi","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1042\/bj1190175","article-title":"Metabolism of the cellular slime mould Dictyostelium discoideum grown in axenic culture","volume":"119","author":"Ashworth","year":"1970","journal-title":"Biochem. J."},{"key":"ref_33","unstructured":"(2021, July 29). Available online: http:\/\/dictybase.org\/techniques\/media\/media.html."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Vogel, E., Pittman, P.B., and Naylor, K. (2019). The FtsZ Homolog, FszB, Inhibits Mitochondrial Dynamics in Dictyostelium discoideum. Cells, 9.","DOI":"10.3390\/cells9010064"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/BF02703333","article-title":"Biochemical basis of the high resistance to oxidative stress in Dictyostelium discoideum","volume":"28","author":"Katoch","year":"2003","journal-title":"J. Biosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5430","DOI":"10.1016\/j.febslet.2007.10.044","article-title":"Tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2","volume":"581","author":"Kim","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6015","DOI":"10.1016\/S0021-9258(18)32365-2","article-title":"Isolation and characterization of the pseudocatalase of Lactobacillus plantarum","volume":"258","author":"Kono","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.bbrc.2018.05.050","article-title":"Catalase inhibition induces pexophagy through ROS accumulation","volume":"501","author":"Lee","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0166-4328(02)00180-8","article-title":"Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats","volume":"136","author":"Alam","year":"2002","journal-title":"Behav. Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0014-4827(74)90210-9","article-title":"Rotenone inhibition of spindle microtubule assembly in mammalian cells","volume":"85","author":"Brinkley","year":"1974","journal-title":"Exp. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10756","DOI":"10.1523\/JNEUROSCI.23-34-10756.2003","article-title":"Mechanism of Toxicity in Rotenone Models of Parkinson\u2019s Disease","volume":"23","author":"Sherer","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_42","first-page":"469","article-title":"Microtubule: A Common Target for Parkin and Parkinson\u2019s Disease Toxins","volume":"12","author":"Feng","year":"2006","journal-title":"Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1432-1033.1996.0623w.x","article-title":"The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites","volume":"238","author":"Chernyak","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1023\/A:1022694131572","article-title":"Mitochondrial implication in accidental and programmed cell death: Apoptosis and necrosis","volume":"29","author":"Zamzami","year":"1997","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nrn1868","article-title":"Expanding insights of mitochondrial dysfunction in Parkinson\u2019s disease","volume":"7","author":"Muqit","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wolf, C., Zimmermann, R., Thaher, O., Bueno, D., W\u00fcllner, V., Sch\u00e4fer, M.K.E., Albrecht, P., and Methner, A. (2019). The Charcot-Marie Tooth Disease Mutation R94Q in MFN2 Decreases ATP Production but Increases Mitochondrial Respiration under Conditions of Mild Oxidative Stress. Cells, 8.","DOI":"10.20944\/preprints201909.0059.v2"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/2147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:48:01Z","timestamp":1760165281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/8\/2147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,20]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cells10082147"],"URL":"https:\/\/doi.org\/10.3390\/cells10082147","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,20]]}}}