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(Elite Ed)"],"abstract":"<jats:p>Background: Mitochondria play a key role in the regulation of inflammatory processes. It is well established that mitochondria contain their own mitochondrial DNA (mtDNA), which displays a substantially higher frequency of polymorphisms compared to the nuclear genome. To maintain mitochondrial functionality, cells employ a quality control mechanism known as mitophagy, which ensures the selective removal of dysfunctional mitochondria. The aim of this study was to investigate the relationship between mitochondrial polymorphisms, the efficiency of dysfunctional mitochondria clearance, and proinflammatory activation of inflammatory cells. Methods: In this study, we used cybrids derived from the THP-1 (human monocytic leukemia cell line) that differed in their mitochondrial genome. Results: Based on the levels of secreted proinflammatory cytokines (tumor necrosis factor (TNF), interleukin-1\u03b2 (IL-1\u03b2), IL-6, IL-8, and C-C motif chemokine ligand 2 (CCL2)), cybrids were divided into two groups: one exhibiting a low and the other a high proinflammatory response. mtDNA sequencing revealed a higher number of polymorphisms in the high proinflammatory response group. Transcriptome analysis showed that signaling pathways associated with mitophagy were downregulated in cells with a high proinflammatory response. Functional assays confirmed that mitophagy was impaired in this group. Conclusions: Increased proinflammatory activity in cybrids correlated with a greater number of mtDNA polymorphisms and with impaired mitophagy. These observations point to an association between mitochondrial genomic variation, reduced mitochondrial quality control, and heightened proinflammatory activation of inflammatory cells. However, the data are associative and do not establish causality. Further mechanistic studies are required to determine whether and how mtDNA polymorphisms and defective mitophagy directly contribute to proinflammatory activation.<\/jats:p>","DOI":"10.31083\/fbe49053","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:24:22Z","timestamp":1790699062000},"source":"Crossref","is-referenced-by-count":0,"title":["Increased mtDNA Polymorphism Level and Defective Mitophagy are Associated With Proinflammatory Activation in THP-1-Based Cybrids"],"prefix":"10.31083","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-2594","authenticated-orcid":true,"given":"Alexander D.","family":"Zhuravlev","sequence":"first","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2082-2429","authenticated-orcid":true,"given":"Nikita G.","family":"Nikiforov","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"},{"name":"Core Facility Center, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia"},{"name":"Laboratory of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-0586","authenticated-orcid":true,"given":"Svetlana S.","family":"Verkhova","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5990-4077","authenticated-orcid":true,"given":"Yegor E","family":"Yegorov","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-4413","authenticated-orcid":true,"given":"Andrey V.","family":"Omelchenko","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-5470","authenticated-orcid":true,"given":"Daria D.","family":"Borodko","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0312-3773","authenticated-orcid":true,"given":"Vasily N.","family":"Sukhorukov","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-5763","authenticated-orcid":true,"given":"Vasily V.","family":"Sinyov","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Pathology, Chazov National Medical Research Center of Cardiology, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7710-2202","authenticated-orcid":true,"given":"Yegor S.","family":"Chegodaev","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2279-0157","authenticated-orcid":true,"given":"Daiana B.","family":"Erdyneeva","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-4681","authenticated-orcid":true,"given":"Alexander N.","family":"Orekhov","sequence":"additional","affiliation":[{"name":"Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"},{"name":"Institute for Atherosclerosis Research, 121609 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Mathers CD, Boerma T, Ma Fat D. 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Lowering effects of four different statins on serum triglyceride level. European Journal of Clinical Pharmacology. 1999; 55: 499\u2013502.","DOI":"10.1007\/s002280050663"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Cholesterol Treatment Trialists' Collaboration. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet (London, England). 2022; 400: 832\u2013845.","DOI":"10.1016\/S0140-6736(22)01545-8"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Aday AW, Ridker PM. Antiinflammatory Therapy in Clinical Care: The CANTOS Trial and Beyond. Frontiers in Cardiovascular Medicine. 2018; 5: 62.","DOI":"10.3389\/fcvm.2018.00062"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biological Chemistry. 2012; 393: 547\u2013564.","DOI":"10.1515\/hsz-2012-0119"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Yang Z, Sun L, Wang H. Identification of mitophagy-related genes with potential clinical utility in myocardial infarction at transcriptional level. Frontiers in Cardiovascular Medicine. 2023; 10: 1166324.","DOI":"10.3389\/fcvm.2023.1166324"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Casanova A, Wevers A, Navarro-Ledesma S, Pruimboom L. Mitochondria: It is all about energy. Frontiers in Physiology. 2023; 14: 1114231.","DOI":"10.3389\/fphys.2023.1114231"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Sazonova MA, Sinyov VV, Ryzhkova AI, Galitsyna EV, Melnichenko AA, Postnov AY, et al. Cybrid Models of Pathological Cell Processes in Different Diseases. Oxidative Medicine and Cellular Longevity. 2018; 2018: 4647214.","DOI":"10.1155\/2018\/4647214"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv. 2013.  (preprint)","DOI":"10.48550\/arXiv.1303.3997"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Wickham H, Averick M, Bryan J, Chang W, McGowan LD, Fran\u00e7ois R, et al. Welcome to the Tidyverse. Journal of Open Source Software. 2019; 4: 1686.","DOI":"10.21105\/joss.01686"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology. 2014; 15: 550.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. 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Journal of Diabetes Research. 2019; 2019: 5184647.","DOI":"10.1155\/2019\/5184647"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Manini TM, Buford TW, Kairalla JA, McDermott MM, Vaz Fragoso CA, Fielding RA, et al. Meta-analysis identifies mitochondrial DNA sequence variants associated with walking speed. GeroScience. 2018; 40: 497\u2013511.","DOI":"10.1007\/s11357-018-0043-x"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Eaaswarkhanth M, Melhem M, Sharma P, Nizam R, Al Madhoun A, Chaubey G, et al. Mitochondrial DNA D-loop sequencing reveals obesity variants in an Arab population. The Application of Clinical Genetics. 2019; 12: 63\u201370.","DOI":"10.2147\/TACG.S198593"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Zarrouk Mahjoub S, Mehri S, Ourda F, Boussaada R, Mechmeche R, Arab SB, et al. Transition m.3308T>C in the ND1 gene is associated with left ventricular hypertrabeculation\/noncompaction. Cardiology. 2011; 118: 153\u2013158.","DOI":"10.1159\/000328002"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Zhu Y, You J, Xu C, Gu X. Associations of mitochondrial DNA 3777-4679 region mutations with maternally inherited essential hypertensive subjects in China. BMC Medical Genetics. 2020; 21: 105.","DOI":"10.1186\/s12881-020-01045-7"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Blok MJ, Spruijt L, de Coo IFM, Schoonderwoerd K, Hendrickx A, Smeets HJ. Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease. Journal of Medical Genetics. 2007; 44: e74.","DOI":"10.1136\/jmg.2006.045716"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Pradeepkiran JA, Reddy PH. Defective mitophagy in Alzheimer's disease. Ageing Research Reviews. 2020; 64: 101191.","DOI":"10.1016\/j.arr.2020.101191"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Bhansali S, Bhansali A, Dhawan V. Favourable metabolic profile sustains mitophagy and prevents metabolic abnormalities in metabolically healthy obese individuals. Diabetology & Metabolic Syndrome. 2017; 9: 99.","DOI":"10.1186\/s13098-017-0298-x"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Lewerissa EI, Nadif Kasri N, Linda K. Epigenetic regulation of autophagy-related genes: Implications for neurodevelopmental disorders. Autophagy. 2024; 20: 15\u201328.","DOI":"10.1080\/15548627.2023.2250217"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Deretic V, Kroemer G. Autophagy in metabolism and quality control: opposing, complementary or interlinked functions? Autophagy. 2022; 18: 283\u2013292.","DOI":"10.1080\/15548627.2021.1933742"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Huang C, Yan S, Zhang Z. Maintaining the balance of TDP-43, mitochondria, and autophagy: a promising therapeutic strategy for neurodegenerative diseases. Translational Neurodegeneration. 2020; 9: 40.","DOI":"10.1186\/s40035-020-00219-w"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Hunt M, Torres M, Bachar-Wikstr\u00f6m E, Wikstr\u00f6m JD. Multifaceted roles of mitochondria in wound healing and chronic wound pathogenesis. Frontiers in Cell and Developmental Biology. 2023; 11: 1252318.","DOI":"10.3389\/fcell.2023.1252318"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Zhunina OA, Yabbarov NG, Grechko AV, Starodubova AV, Ivanova E, Nikiforov NG, et al. The Role of Mitochondrial Dysfunction in Vascular Disease, Tumorigenesis, and Diabetes. Frontiers in Molecular Biosciences. 2021; 8: 671908.","DOI":"10.3389\/fmolb.2021.671908"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Elorza AA, Soffia JP. mtDNA Heteroplasmy at the Core of Aging-Associated Heart Failure. An Integrative View of OXPHOS and Mitochondrial Life Cycle in Cardiac Mitochondrial Physiology. Frontiers in Cell and Developmental Biology. 2021; 9: 625020.","DOI":"10.3389\/fcell.2021.625020"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Pollock L, Jardine J, Urb\u00e9 S, Clague MJ. The PINK1 repertoire: Not just a one trick pony. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology. 2021; 43: e2100168.","DOI":"10.1002\/bies.202100168"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Borsche M, K\u00f6nig IR, Delcambre S, Petrucci S, Balck A, Br\u00fcggemann N, et al. Mitochondrial damage-associated inflammation highlights biomarkers in PRKN\/PINK1 parkinsonism. Brain: a Journal of Neurology. 2020; 143: 3041\u20133051.","DOI":"10.1093\/brain\/awaa246"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Eskelinen EL. Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Molecular Aspects of Medicine. 2006; 27: 495\u2013502.","DOI":"10.1016\/j.mam.2006.08.005"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Zhao H, Chen H, Xiaoyin M, Yang G, Hu Y, Xie K, et al. Autophagy Activation Improves Lung Injury and Inflammation in Sepsis. Inflammation. 2019; 42: 426\u2013439.","DOI":"10.1007\/s10753-018-00952-5"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Sawabe M, Tanaka M, Chida K, Arai T, Nishigaki Y, Fuku N, et al. Mitochondrial haplogroups A and M7a confer a genetic risk for coronary atherosclerosis in the Japanese elderly: an autopsy study of 1,536 patients. Journal of Atherosclerosis and Thrombosis. 2011; 18: 166\u2013175.","DOI":"10.5551\/jat.6742"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Wei R, Ni Y, Bazeley P, Grandhi S, Wang J, Li ST, et al. Mitochondrial DNA Content Is Linked to Cardiovascular Disease Patient Phenotypes. Journal of the American Heart Association. 2021; 10: e018776.","DOI":"10.1161\/JAHA.120.018776"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Yu E, Calvert PA, Mercer JR, Harrison J, Baker L, Figg NL, et al. Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Circulation. 2013; 128: 702\u2013712.","DOI":"10.1161\/CIRCULATIONAHA.113.002271"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Piotrowska-Nowak A, Elson JL, Sobczyk-Kopciol A, Piwonska A, Puch-Walczak A, Drygas W, et al. New mtDNA Association Model, MutPred Variant Load, Suggests Individuals With Multiple Mildly Deleterious mtDNA Variants Are More Likely to Suffer From Atherosclerosis. Frontiers in Genetics. 2019; 9: 702.","DOI":"10.3389\/fgene.2018.00702"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Jayatunga DPW, Hone E, Khaira H, Lunelli T, Singh H, Guillemin GJ, et al. Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer's Disease. Nutrients. 2021; 13: 3744.","DOI":"10.3390\/nu13113744"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Luo T, Jia X, Feng WD, Wang JY, Xie F, Kong LD, et al. Bergapten inhibits NLRP3 inflammasome activation and pyroptosis via promoting mitophagy. Acta Pharmacologica Sinica. 2023; 44: 1867\u20131878.","DOI":"10.1038\/s41401-023-01094-7"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Liu M, Lu J, Yang S, Chen Y, Yu J, Guan S. Alliin alleviates LPS-induced pyroptosis via promoting mitophagy in THP-1 macrophages and mice. 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