{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:08:29Z","timestamp":1789542509509,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["NSTC113-2320-B-038-037"],"award-info":[{"award-number":["NSTC113-2320-B-038-037"]}]},{"award":["NSTC113-2320-B-038-037"],"award-info":[{"award-number":["NSTC113-2320-B-038-037"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Global plastic production has led to widespread contamination by micro- and nanoplastics, with polystyrene nanoplastics (PSNPs) increasingly being detected in human biological samples, including blood and cardiac tissue. Given the critical role of mitochondria in cardiac energy metabolism, this study investigated whether 100 nm PSNPs interact with mitochondria and affect mitochondrial function in H9c2 cardiomyoblasts. Cellular uptake and intracellular distribution were examined, followed by an evaluation of mitochondrial ultrastructure, intracellular and mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential, mitochondrial dynamics and mitophagy-related gene expression, mitochondrial DNA copy number, and metabolic function. PSNPs were internalized but did not directly localize to mitochondria within 24 h. No significant cytotoxicity, increase in intracellular or mitochondrial ROS production, or alteration in basal metabolic activity was observed. However, PSNP exposure resulted in intracellular accumulation, an altered mitochondrial ultrastructure characterized by crista loosening and vacuole-like structural changes. These changes were accompanied by reduced mitochondrial membrane potential; the upregulation of mitochondrial dynamics-related genes, including optic atrophy 1 (Opa1) and dynamin-related protein 1 (Drp1); the suppression of PTEN-induced kinase 1 (PINK1)\/Parkin RBR E3 ubiquitin protein ligase (Parkin)-mediated mitophagy-related genes; and decreased maximal respiratory capacity. Lactate production and the extracellular acidification rate remained unchanged, suggesting that compensatory glycolysis was not activated. These findings indicate that PSNP exposure induces early mitochondrial structural and functional alterations without substantial cell damage, suggesting a potential reduction in cardiac adaptive capacity under PSNP-induced stress conditions.<\/jats:p>","DOI":"10.3390\/antiox15070801","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polystyrene Nanoplastics Induce Early Mitochondrial Dysfunction in H9c2 Cardiomyoblasts Without Substantial Cell Damage"],"prefix":"10.3390","volume":"15","author":[{"given":"Ming-Hung","family":"Shen","sequence":"first","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Hsuan","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Yu","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddy","family":"Owaga","sequence":"additional","affiliation":[{"name":"Institute of Food Bioresources Technology, Dedan Kimathi University of Technology, Nyeri 10143, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Sheng","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center of Nutritional Medicine, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Hong","family":"Hsieh","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Research Center of Nutritional Medicine, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100220","DOI":"10.1016\/j.clema.2024.100220","article-title":"The world of plastic waste: A review","volume":"11","author":"Pilapitiya","year":"2024","journal-title":"Clean. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"126770","DOI":"10.1016\/j.jhazmat.2021.126770","article-title":"Size-dependent effects of polystyrene nanoplastics on autophagy response in human umbilical vein endothelial cells","volume":"421","author":"Lu","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106061","DOI":"10.1016\/j.isci.2023.106061","article-title":"Recent insights into uptake, toxicity, and molecular targets of microplastics and nanoplastics relevant to human health impacts","volume":"26","author":"Khan","year":"2023","journal-title":"iScience"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Masseroni, A., Rizzi, C., Urani, C., and Villa, S. (2022). Nanoplastics: Status and Knowledge Gaps in the Finalization of Environmental Risk Assessments. Toxics, 10.","DOI":"10.3390\/toxics10050270"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"46687","DOI":"10.1038\/srep46687","article-title":"Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure","volume":"7","author":"Deng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.scitotenv.2018.03.051","article-title":"Polystyrene microplastics induce gut microbiota dysbiosis and hepatic lipid metabolism disorder in mice","volume":"631\u2013632","author":"Lu","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119060","DOI":"10.1016\/j.ecoenv.2025.119060","article-title":"Polystyrene nanoplastics induced lung injury in mice: Insights into lung metabolic disorders","volume":"303","author":"Wang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liu, Y.Y., Liu, J., Wu, H., Zhang, Q., Tang, X.R., Li, D., Li, C.S., Liu, Y., Cao, A., and Wang, H. (2022). Endocytosis, Distribution, and Exocytosis of Polystyrene Nanoparticles in Human Lung Cells. Nanomaterials, 13.","DOI":"10.3390\/nano13010084"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107199","DOI":"10.1016\/j.envint.2022.107199","article-title":"Discovery and quantification of plastic particle pollution in human blood","volume":"163","author":"Leslie","year":"2022","journal-title":"Environ. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10911","DOI":"10.1021\/acs.est.2c07179","article-title":"Detection of Various Microplastics in Patients Undergoing Cardiac Surgery","volume":"57","author":"Yang","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107662","DOI":"10.1016\/j.envint.2022.107662","article-title":"Micro- and nanoplastics: A new cardiovascular risk factor?","volume":"171","author":"Zhu","year":"2023","journal-title":"Environ. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123430","DOI":"10.1016\/j.jhazmat.2020.123430","article-title":"Polystyrene microplastics induced male reproductive toxicity in mice","volume":"401","author":"Jin","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Iannuzzi, G.L., D\u2019Alto, M., Bosso, G., Montella, A.P., D\u2019Oria, V., Pellegrino, L., Boccaforno, G., Masi, A., Orlando, A., and Franco, R. (2025). Microplastics, Nanoplastics and Heart Contamination: The Hidden Threat. J. Clin. Med., 14.","DOI":"10.3390\/jcm14217618"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.freeradbiomed.2017.02.032","article-title":"The role of mitochondria in cardiac development and protection","volume":"106","author":"Pohjoismaki","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tirichen, H., Yaigoub, H., Xu, W., Wu, C., Li, R., and Li, Y. (2021). Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.627837"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bisaccia, G., Ricci, F., Gallina, S., Di Baldassarre, A., and Ghinassi, B. (2021). Mitochondrial Dysfunction and Heart Disease: Critical Appraisal of an Overlooked Association. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020614"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"C723","DOI":"10.1152\/ajpcell.00462.2010","article-title":"A practical guide to evaluating colocalization in biological microscopy","volume":"300","author":"Dunn","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9316","DOI":"10.3390\/cimb45110583","article-title":"Comparison of the Protective Effects of Nebivolol and Metoprolol against LPS-Induced Injury in H9c2 Cardiomyoblasts","volume":"45","author":"Gul","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115577","DOI":"10.1016\/j.taap.2021.115577","article-title":"Mitochondrial dynamics imbalance and mitochondrial dysfunction contribute to the molecular cardiotoxic effects of lenvatinib","volume":"423","author":"Boran","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41419-021-03821-6","article-title":"LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1\/Parkin signaling during obesity","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jep.2019.03.033","article-title":"Mitochondrial dynamics modulation as a critical contribution for Shenmai injection in attenuating hypoxia\/reoxygenation injury","volume":"237","author":"Yu","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13046-022-02262-z","article-title":"Increased Drp1 promotes autophagy and ESCC progression by mtDNA stress mediated cGAS-STING pathway","volume":"41","author":"Li","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/jcb.21625","article-title":"Maintenance of mitochondrial DNA copy number and expression are essential for preservation of mitochondrial function and cell growth","volume":"103","author":"Jeng","year":"2008","journal-title":"J. Cell Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"123923","DOI":"10.1016\/j.jhazmat.2020.123923","article-title":"Perturbation of calcium homeostasis and multixenobiotic resistance by nanoplastics in the ciliate Tetrahymena thermophila","volume":"403","author":"Wu","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Domenech, J., de Britto, M., Velazquez, A., Pastor, S., Hernandez, A., Marcos, R., and Cortes, C. (2021). Long-Term Effects of Polystyrene Nanoplastics in Human Intestinal Caco-2 Cells. Biomolecules, 11.","DOI":"10.3390\/biom11101442"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19321","DOI":"10.1039\/C3RA46869K","article-title":"Role of membrane disturbance and oxidative stress in the mode of action underlying the toxicity of differently charged polystyrene nanoparticles","volume":"4","author":"Bhattacharjee","year":"2014","journal-title":"RSC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12483","DOI":"10.1021\/acs.est.2c03980","article-title":"Metabolomics Reveal Nanoplastic-Induced Mitochondrial Damage in Human Liver and Lung Cells","volume":"56","author":"Lin","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12989-015-0091-7","article-title":"Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: Robust response of alveolar type 1 epithelial cells","volume":"12","author":"Ruenraroengsak","year":"2015","journal-title":"Part. Fibre Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.17219\/pim\/177127","article-title":"Alteration of zeta potential and cell viability in rat-derived L6 skeletal muscle cells and H9c2 cardiomyocytes: A study with submicron polystyrene particles","volume":"54","author":"Kotynska","year":"2024","journal-title":"Polim. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"146523","DOI":"10.1016\/j.scitotenv.2021.146523","article-title":"Cellular internalization and release of polystyrene microplastics and nanoplastics","volume":"779","author":"Liu","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114796","DOI":"10.1016\/j.ecoenv.2023.114796","article-title":"Exposure to nanoplastics induces mitochondrial impairment and cytomembrane destruction in Leydig cells","volume":"255","author":"Sun","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133142","DOI":"10.1016\/j.jhazmat.2023.133142","article-title":"Nanoplastic propels diet-induced NAFL to NASH via ER-mitochondrial tether-controlled redox switch","volume":"465","author":"Wei","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Joubert, F., and Puff, N. (2021). Mitochondrial Cristae Architecture and Functions: Lessons from Minimal Model Systems. Membranes, 11.","DOI":"10.3390\/membranes11070465"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"128485","DOI":"10.1016\/j.jhazmat.2022.128485","article-title":"Toxic effects of nanoplastics with different sizes and surface charges on epithelial-to-mesenchymal transition in A549 cells and the potential toxicological mechanism","volume":"430","author":"Halimu","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12951-024-02375-x","article-title":"Nanoplastics causes heart aging\/myocardial cell senescence through the Ca2+\/mtDNA\/cGAS-STING signaling cascade","volume":"22","author":"Wang","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.mito.2019.06.003","article-title":"Linking mitochondrial dynamics, cristae remodeling and supercomplex formation: How mitochondrial structure can regulate bioenergetics","volume":"49","author":"Baker","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"154002","DOI":"10.1016\/j.tox.2024.154002","article-title":"Exposure to polystyrene nanoplastics promotes premature cellular senescence through mitochondrial ROS production and dysfunction in pre-differentiated skeletal myoblasts","volume":"510","author":"Bang","year":"2025","journal-title":"Toxicology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"47921","DOI":"10.1007\/s11356-021-13911-9","article-title":"Polystyrene microplastics induce blood-testis barrier disruption regulated by the MAPK-Nrf2 signaling pathway in rats","volume":"28","author":"Li","year":"2021","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bu, W., Cui, Y., Jin, Y., Wang, X., Jiang, M., Huang, R., Egbobe, J.O., Zhao, X., and Tang, J. (2024). Unmasking the Invisible Threat: Biological Impacts and Mechanisms of Polystyrene Nanoplastics on Cells. Toxics, 12.","DOI":"10.3390\/toxics12120908"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kik, K., Bukowska, B., Krokosz, A., and Sicinska, P. (2021). Oxidative Properties of Polystyrene Nanoparticles with Different Diameters in Human Peripheral Blood Mononuclear Cells (In Vitro Study). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094406"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1186\/s12951-025-03503-x","article-title":"Polystyrene microplastics exacerbate mitophagy through mitochondrial dysfunction in the duck lung","volume":"23","author":"Gu","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113520","DOI":"10.1016\/j.ecoenv.2022.113520","article-title":"Polystyrene microplastics induce mitochondrial damage in mouse GC-2 cells","volume":"237","author":"Liu","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110502","DOI":"10.1016\/j.cbi.2023.110502","article-title":"ROS and DRP1 interactions accelerate the mitochondrial injury induced by polystyrene nanoplastics in human liver HepG2 cells","volume":"379","author":"Li","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"124935","DOI":"10.1016\/j.envpol.2024.124935","article-title":"Disturbance of mitochondrial dynamics led to spermatogenesis disorder in mice exposed to polystyrene micro- and nanoplastics","volume":"362","author":"Zhao","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.mito.2019.08.001","article-title":"Limited predictive value of TFAM in mitochondrial biogenesis","volume":"49","author":"Kozhukhar","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1089\/ars.2010.3779","article-title":"The interplay between mitochondrial dynamics and mitophagy","volume":"14","author":"Twig","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"139232","DOI":"10.1016\/j.jhazmat.2025.139232","article-title":"Polystyrene nanoplastics promote muscle cell senescence through microtubule hyper-stabilization-mediated mitophagy dysfunction and cGAS-Sting activation","volume":"496","author":"Cui","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e41298","DOI":"10.1016\/j.heliyon.2024.e41298","article-title":"Polystyrene nanoparticles induce DNA damage and apoptosis in HeLa cells","volume":"11","author":"Feola","year":"2025","journal-title":"Heliyon"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Saenen, N.D., Witters, M.S., Hantoro, I., Tejeda, I., Ethirajan, A., Van Belleghem, F., and Smeets, K. (2023). Polystyrene Microplastics of Varying Sizes and Shapes Induce Distinct Redox and Mitochondrial Stress Responses in a Caco-2 Monolayer. Antioxidants, 12.","DOI":"10.3390\/antiox12030739"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ren, L., Chen, X., Chen, X., Li, J., Cheng, B., and Xia, J. (2020). Mitochondrial Dynamics: Fission and Fusion in Fate Determination of Mesenchymal Stem Cells. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.580070"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.taap.2008.08.013","article-title":"Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro","volume":"233","author":"Dykens","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/7\/801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:19:01Z","timestamp":1783052341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/7\/801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":51,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["antiox15070801"],"URL":"https:\/\/doi.org\/10.3390\/antiox15070801","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}