{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:49:21Z","timestamp":1786121361033,"version":"build-2736575974"},"reference-count":82,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"crossref","award":["2019\/35\/O\/NZ5\/02502"],"award-info":[{"award-number":["2019\/35\/O\/NZ5\/02502"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2019\/35\/O\/NZ5\/02502"],"award-info":[{"award-number":["2019\/35\/O\/NZ5\/02502"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial metabolic disorder that is strongly associated with mitochondrial dysfunction and oxidative stress, which may potentially compromise the integrity of mitochondrial DNA (mtDNA). However, the role of the base excision repair (BER) pathway\u2014the main mechanism responsible for repairing oxidative lesions in mitochondria\u2014and maintaining mtDNA stability in MASLD remains poorly understood. Here, we analyzed total mRNA expression levels of key BER components in whole-blood samples, along with mitochondrial protein levels of the selected components. Additionally, we assessed the mtDNA copy number and the damage of mtDNA and nuclear DNA in peripheral leukocytes from MASLD patients and healthy controls. We found that MASLD patients differed from controls in mtDNA and nuclear DNA damage, mtDNA copy number, and selected BER-related markers. However, because the MASLD and control groups also differed substantially in age and BMI, these molecular differences should be interpreted as potentially being associated with age- and BMI-related metabolic status rather than attributable to MASLD alone. While several BER-related genes were downregulated at the mRNA level, the corresponding mitochondrial protein levels were not consistently decreased in MASLD (ProteomeXchange: PXD075974), indicating a discordance between transcriptional and protein-level regulation. These results suggest that altered mitochondrial BER and mtDNA instability in peripheral leukocytes may reflect the combined influence of MASLD, aging, obesity, and broader metabolic dysfunction.<\/jats:p>","DOI":"10.3390\/cells15151415","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:14:46Z","timestamp":1785917686000},"page":"1415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Mitochondrial Base Excision Repair and Mitochondrial DNA Instability in Peripheral Leukocytes of Patients with MASLD"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8140-3853","authenticated-orcid":false,"given":"Sylwia","family":"Zi\u00f3\u0142kowska","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0609-9657","authenticated-orcid":false,"given":"Marcin","family":"Kosmalski","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9373-4008","authenticated-orcid":false,"given":"Bianka","family":"\u015awiderska","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4331-665X","authenticated-orcid":false,"given":"Agnieszka","family":"Szczypiorowska","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Jarmusz","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Ejsmont","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6414-7111","authenticated-orcid":false,"given":"Adam Marek","family":"Wr\u00f3blewski","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6052-3557","authenticated-orcid":false,"given":"Janusz","family":"Szemraj","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"},{"name":"Faculty of Medicine, Lazarski University, 02-662 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadeusz","family":"Pietras","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-5233","authenticated-orcid":false,"given":"Aleksandra","family":"Jab\u0142kowska","sequence":"additional","affiliation":[{"name":"Department of Infectious and Liver Diseases, Medical University of Lodz, 91-347 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5146-5225","authenticated-orcid":false,"given":"Piotr","family":"Czarny","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., Kassir, R., Singhal, R., Mahawar, K., and Ramnarain, D. (2022). Non-Alcoholic Fatty Liver Disease (NAFLD): A Review of Pathophysiology, Clinical Management and Effects of Weight Loss. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-00980-1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and Disease Consequences of Nonalcoholic Fatty Liver Disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ziolkowska, S., Binienda, A., Jab\u0142kowski, M., Szemraj, J., and Czarny, P. (2021). The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011128"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9604","DOI":"10.1093\/nar\/gks722","article-title":"Histone Dosage Regulates DNA Damage Sensitivity in a Checkpoint-Independent Manner by the Homologous Recombination Pathway","volume":"40","author":"Liang","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1196\/annals.1338.023","article-title":"Oxidative Damage in Mitochondrial DNA Is Not Extensive","volume":"1042","author":"Lim","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gohil, D., Sarker, A.H., and Roy, R. (2023). Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814186"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hsiao, P.-J., Hsieh, T.-J., Kuo, K.-K., Hung, W.-W., Tsai, K.-B., Yang, C.-H., Yu, M.-L., and Shin, S.-J. (2008). Pioglitazone Retrieves Hepatic Antioxidant DNA Repair in a Mice Model of High Fat Diet. BMC Mol. Biol., 9.","DOI":"10.1186\/1471-2199-9-82"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1002\/jat.3117","article-title":"The Effect of a Methyl-Deficient Diet on the Global DNA Methylation and the DNA Methylation Regulatory Pathways","volume":"35","author":"Takumi","year":"2015","journal-title":"J. Appl. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"G1070","DOI":"10.1152\/ajpgi.00228.2004","article-title":"Oxidative DNA Damage and DNA Repair Enzyme Expression Are Inversely Related in Murine Models of Fatty Liver Disease","volume":"287","author":"Gao","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kosmalski, M., Frankowski, R., Zi\u00f3\u0142kowska, S., R\u00f3\u017cycka-Kosmalska, M., and Pietras, T. (2023). What\u2019s New in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD). J. Clin. Med., 12.","DOI":"10.3390\/jcm12051852"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Panera, N., Braghini, M.R., Crudele, A., Smeriglio, A., Bianchi, M., Condorelli, A.G., Nobili, R., Conti, L.A., De Stefanis, C., and Lioci, G. (2022). Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis. Nutrients, 14.","DOI":"10.3390\/nu14183791"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/hep4.1696","article-title":"Ipragliflozin Improves the Hepatic Outcomes of Patients with Diabetes with NAFLD","volume":"6","author":"Takahashi","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1007\/s12325-020-01498-5","article-title":"Effect of Empagliflozin on Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease Without Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"37","author":"Taheri","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis","volume":"390","author":"Harrison","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108984","DOI":"10.1016\/j.diabres.2021.108984","article-title":"Pioglitazone Even at Low Dosage Improves NAFLD in Type 2 Diabetes: Clinical and Pathophysiological Insights from a Subgroup of the TOSCA.IT Randomised Trial","volume":"178","author":"Russo","year":"2021","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","article-title":"Determination of Stable Housekeeping Genes, Differentially Regulated Target Genes and Sample Integrity: BestKeeper--Excel-Based Tool Using Pair-Wise Correlations","volume":"26","author":"Pfaffl","year":"2004","journal-title":"Biotechnol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104301","DOI":"10.1016\/j.ebiom.2022.104301","article-title":"Lung Mitochondrial DNA Copy Number, Inflammatory Biomarkers, Gene Transcription and Gene Methylation in Vapers and Smokers","volume":"85","author":"Mori","year":"2022","journal-title":"eBioMedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1093\/nar\/gkp1082","article-title":"Analysis of Differential DNA Damage in the Mitochondrial Genome Employing a Semi-Long Run Real-Time PCR Approach","volume":"38","author":"Rothfuss","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/15622975.2019.1588993","article-title":"Mitochondrial DNA Copy Number, Damage, Repair and Degradation in Depressive Disorder","volume":"21","author":"Czarny","year":"2020","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_21","first-page":"159","article-title":"Measuring Oxidative MtDNA Damage and Repair Using Quantitative PCR","volume":"197","author":"Santos","year":"2002","journal-title":"Methods Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41596-018-0082-x","article-title":"Single-Pot, Solid-Phase-Enhanced Sample Preparation for Proteomics Experiments","volume":"14","author":"Hughes","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5203","DOI":"10.1038\/s41598-023-32549-w","article-title":"Enhanced Mitochondrial Oxidative Metabolism in Peripheral Blood Mononuclear Cells Is Associated with Fatty Liver in Obese Young Adults","volume":"13","author":"Shirakawa","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/joim.13147","article-title":"Liver Mitochondrial DNA Damage and Genetic Variability of Cytochrome b\u2014A Key Component of the Respirasome\u2014Drive the Severity of Fatty Liver Disease","volume":"289","author":"Pirola","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1111\/jgh.13318","article-title":"Unique Features Associated with Hepatic Oxidative DNA Damage and DNA Methylation in Non-Alcoholic Fatty Liver Disease","volume":"31","author":"Nishida","year":"2016","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lee, A.H., Oh, J.H., Kim, H.S., Shin, J.H., Yoon, E.L., and Jun, D.W. (2022). Peripheral Blood Mononuclear Cell Mitochondrial Copy Number and Adenosine Triphosphate Inhibition Test in NAFLD. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.967848"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e40774","DOI":"10.5812\/hepatmon.40774","article-title":"Liver Mitochondrial DNA Copy Number and Deletion Levels May Contribute to Nonalcoholic Fatty Liver Disease Susceptibility","volume":"16","author":"Kamfar","year":"2016","journal-title":"Hepat. Mon."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Houshmand, M., Zeinali, V., Hosseini, A., Seifi, A., Danaei, B., and Kamfar, S. (2023). Investigation of FGF21 MRNA Levels and Relative Mitochondrial DNA Copy Number Levels and Their Relation in Nonalcoholic Fatty Liver Disease: A Case-Control Study. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1203019"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Malik, A.N., Sim\u00f5es, I.C.M., Rosa, H.S., Khan, S., Karkucinska-Wieckowska, A., and Wieckowski, M.R. (2019). A Diet Induced Maladaptive Increase in Hepatic Mitochondrial DNA Precedes OXPHOS Defects and May Contribute to Non-Alcoholic Fatty Liver Disease. Cells, 8.","DOI":"10.3390\/cells8101222"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"a012641","DOI":"10.1101\/cshperspect.a012641","article-title":"The Maintenance of Mitochondrial DNA Integrity\u2014Critical Analysis and Update","volume":"5","author":"Alexeyev","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rong, Z., Tu, P., Xu, P., Sun, Y., Yu, F., Tu, N., Guo, L., and Yang, Y. (2021). The Mitochondrial Response to DNA Damage. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.669379"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zi\u00f3\u0142kowska, S., Kosmalski, M., Ko\u0142odziej, \u0141., Jab\u0142kowska, A., Szemraj, J.Z., Pietras, T., Jab\u0142kowski, M., and Czarny, P.L. (2023). Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411307"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"ugae006","DOI":"10.1093\/narmme\/ugae006","article-title":"Frequencies and Spectra of Aflatoxin B1-Induced Mutations in Liver Genomes of NEIL1-Deficient Mice as Revealed by Duplex Sequencing","volume":"1","author":"Minko","year":"2024","journal-title":"NAR Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1073\/pnas.0507444103","article-title":"The Metabolic Syndrome Resulting from a Knockout of the NEIL1 DNA Glycosylase","volume":"103","author":"Vartanian","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1042\/BST20200250","article-title":"Post-Transcriptional Control of Mitochondrial Protein Composition in Changing Environmental Conditions","volume":"48","author":"Tsuboi","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8403","DOI":"10.1093\/nar\/gkt635","article-title":"Transcriptional Regulation of Human DNA Repair Genes Following Genotoxic Stress: Trigger Mechanisms, Inducible Responses and Genotoxic Adaptation","volume":"41","author":"Christmann","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sampath, H., Vartanian, V., Rollins, M.R., Sakumi, K., Nakabeppu, Y., and Lloyd, R.S. (2012). 8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Increases Susceptibility to Obesity and Metabolic Dysfunction. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051697"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yuzefovych, L.V., Noh, H.L., Suk, S., Schuler, A.M., Mulekar, M.S., Pastukh, V.M., Kim, J.K., and Rachek, L.I. (2024). Mitochondria-Targeted DNA Repair Glycosylase HOGG1 Protects Against HFD-Induced Liver Oxidative Mitochondrial DNA Damage and Insulin Resistance in OGG1-Deficient Mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212168"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Komakula, S.S.B., Blaze, B., Ye, H., Dobrzyn, A., and Sampath, H. (2021). A Novel Role for the DNA Repair Enzyme 8-Oxoguanine DNA Glycosylase in Adipogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031152"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14886","DOI":"10.1038\/s41598-018-33151-1","article-title":"The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue","volume":"8","author":"Komakula","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"103880","DOI":"10.1016\/j.dnarep.2025.103880","article-title":"The Role of DNA Repair Deficiency in Lipid Accumulation: A Proof-of-Concept Study","volume":"152","author":"Tu","year":"2025","journal-title":"DNA Repair"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5925","DOI":"10.1007\/s00018-021-03887-7","article-title":"Sensing, Signaling and Surviving Mitochondrial Stress","volume":"78","author":"Eckl","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.15698\/mic2014.01.127","article-title":"Mitochondrial Protein Import under Kinase Surveillance","volume":"1","author":"Meisinger","year":"2014","journal-title":"Microb. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1093\/nar\/gkt076","article-title":"Mammalian Base Excision Repair: The Forgotten Archangel","volume":"41","author":"Dianov","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s10735-020-09939-9","article-title":"High Nuclear Expression of APE1 Correlates with Unfavorable Prognosis and Promotes Tumor Growth in Hepatocellular Carcinoma","volume":"52","author":"Lu","year":"2021","journal-title":"J. Mol. Histol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jhep.2016.11.020","article-title":"PARP1-Mediated PPAR\u03b1 Poly(ADP-Ribosyl)Ation Suppresses Fatty Acid Oxidation in Non-Alcoholic Fatty Liver Disease","volume":"66","author":"Huang","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/carcin\/bgz104","article-title":"Targeting PARP and Autophagy Evoked Synergistic Lethality in Hepatocellular Carcinoma","volume":"41","author":"Zai","year":"2020","journal-title":"Carcinogenesis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101117","DOI":"10.1016\/j.plipres.2021.101117","article-title":"PARPs in Lipid Metabolism and Related Diseases","volume":"84","author":"Gupte","year":"2021","journal-title":"Prog. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.cmet.2011.03.004","article-title":"PARP-1 Inhibition Increases Mitochondrial Metabolism through SIRT1 Activation","volume":"13","author":"Bai","year":"2011","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1002\/hep.26763","article-title":"Poly (ADP-Ribose) Polymerase-1 Is a Key Mediator of Liver Inflammation and Fibrosis","volume":"59","author":"Mukhopadhyay","year":"2014","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jhep.2016.10.023","article-title":"PARP Inhibition Protects against Alcoholic and Non-Alcoholic Steatohepatitis","volume":"66","author":"Mukhopadhyay","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1038\/emm.2014.42","article-title":"APE1\/Ref-1 as an Emerging Therapeutic Target for Various Human Diseases: Phytochemical Modulation of Its Functions","volume":"46","author":"Thakur","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1002\/jcb.25103","article-title":"Base Excision Repair in the Mitochondria","volume":"116","author":"Prakash","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e0139","DOI":"10.1097\/HC9.0000000000000139","article-title":"Clinical Spectrum and Genetic Causes of Mitochondrial Hepatopathy Phenotype in Children","volume":"7","author":"Squires","year":"2023","journal-title":"Hepatol. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e70112","DOI":"10.1002\/jimd.70112","article-title":"Liver Involvement in POLG Disease\u2014A Multicentre Cohort Study of 202 Patients","volume":"48","author":"Kristensen","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e200167","DOI":"10.1212\/NXG.0000000000200167","article-title":"Distinct Clinical Courses and Shortened Lifespans in Childhood-Onset DNA Polymerase Gamma Deficiency","volume":"10","author":"Gaignard","year":"2024","journal-title":"Neurol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1111\/epi.13508","article-title":"Epilepsy Due to Mutations in the Mitochondrial Polymerase Gamma (POLG) Gene: A Clinical and Molecular Genetic Review","volume":"57","author":"Anagnostou","year":"2016","journal-title":"Epilepsia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9924","DOI":"10.1073\/pnas.152321699","article-title":"Haploinsufficiency of Flap Endonuclease (Fen1) Leads to Rapid Tumor Progression","volume":"99","author":"Kucherlapati","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5346","DOI":"10.1128\/MCB.23.15.5346-5353.2003","article-title":"Proliferation Failure and Gamma Radiation Sensitivity of Fen1 Null Mutant Mice at the Blastocyst Stage","volume":"23","author":"Larsen","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/j.1464-410X.2006.06224.x","article-title":"Flap Endonuclease 1 Is Overexpressed in Prostate Cancer and Is Associated with a High Gleason Score","volume":"98","author":"Lam","year":"2006","journal-title":"BJU Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1093\/nar\/gkl492","article-title":"Differential Recruitment of DNA Ligase I and III to DNA Repair Sites","volume":"34","author":"Mortusewicz","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41419-020-2295-5","article-title":"Hepatocyte Caveolin-1 Modulates Metabolic Gene Profiles and Functions in Non-Alcoholic Fatty Liver Disease","volume":"11","author":"Han","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/ng0896-489","article-title":"DNA Ligase I Is Required for Fetal Liver Erythropoiesis but Is Not Essential for Mammalian Cell Viability","volume":"13","author":"Bentley","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.31557\/APJCP.2025.26.4.1385","article-title":"Genotype and Association of XRCC1 Gene with Liver Disease in Chronic Hcv Patients","volume":"26","author":"Babaresh","year":"2025","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"03946320241265263","DOI":"10.1177\/03946320241265263","article-title":"Association of XRCC1 p. Arg194Trp Gene Polymorphism with the Risk of Hepatocellular Carcinoma in HCV Egyptian Population: A Pilot Case-Control Study","volume":"38","author":"Ghorab","year":"2024","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.1002\/jmv.27217","article-title":"Genetic Variants of APEX1 p.Asp148Glu and XRCC1 p.Gln399Arg with the Susceptibility of Hepatocellular Carcinoma","volume":"93","author":"Saad","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.31557\/APJCP.2025.26.6.2109","article-title":"Association of XRCC1 Gene Polymorphism with an Increased Risk of Hepatocellular Carcinoma in the Peshawar Population","volume":"26","author":"Hassen","year":"2025","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5751939","DOI":"10.1155\/2020\/5751939","article-title":"Evaluation of X-Ray Repair Cross-Complementing Family Members as Potential Biomarkers for Predicting Progression and Prognosis in Hepatocellular Carcinoma","volume":"2020","author":"Mei","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1089\/dna.2017.3664","article-title":"The Relationship Between Single-Nucleotide Polymorphisms, the Expression of DNA Damage Response Genes, and Hepatocellular Carcinoma in a Polish Population","volume":"36","author":"Krupa","year":"2017","journal-title":"DNA Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41467-020-20780-2","article-title":"Endonuclease G Promotes Autophagy by Suppressing MTOR Signaling and Activating the DNA Damage Response","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.1038\/s41467-023-41757-x","article-title":"Cytoplasmic Endonuclease G Promotes Nonalcoholic Fatty Liver Disease via MTORC2-AKT-ACLY and Endoplasmic Reticulum Stress","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e2411298122","DOI":"10.1073\/pnas.2411298122","article-title":"Endonuclease G Promotes Hepatic Mitochondrial Respiration by Selectively Increasing Mitochondrial TRNAThr Production","volume":"122","author":"Xu","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"14959","DOI":"10.1038\/ncomms14959","article-title":"A Domain in Human EXOG Converts Apoptotic Endonuclease to DNA-Repair Exonuclease","volume":"8","author":"Szymanski","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"23543","DOI":"10.1021\/jacs.2c10558","article-title":"Human EXOG Possesses Strong AP Hydrolysis Activity: Implication on Mitochondrial DNA Base Excision Repair","volume":"144","author":"Szymanski","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"gkaf099","DOI":"10.1093\/nar\/gkaf099","article-title":"Mitochondrial Exonuclease EXOG Supports DNA Integrity by the Removal of Single-Stranded DNA Flaps","volume":"53","author":"Karlowicz","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1007\/s11892-014-0548-3","article-title":"Beyond HbA1c and Glucose: The Role of Nontraditional Glycemic Markers in Diabetes Diagnosis, Prognosis, and Management","volume":"14","author":"Parrinello","year":"2014","journal-title":"Curr. Diab. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"S150","DOI":"10.3350\/cmh.2022.0362","article-title":"Noninvasive Serum Biomarkers for Liver Steatosis in Nonalcoholic Fatty Liver Disease: Current and Future Developments","volume":"29","author":"Ahn","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gherghina, M.E., Peride, I., Tiglis, M., Neagu, T.P., Niculae, A., and Checherita, I.A. (2022). Uric Acid and Oxidative Stress\u2014Relationship with Cardiovascular, Metabolic, and Renal Impairment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063188"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"0912","DOI":"10.34133\/research.0912","article-title":"Mitochondria Metabolism Regulates Glucose\u2013Lipid Homeostasis in Neurodegenerative Diseases","volume":"8","author":"Huang","year":"2025","journal-title":"Research"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e70132","DOI":"10.1002\/edm2.70132","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Mechanisms, Clinical Implications and Therapeutic Advances","volume":"8","author":"Miller","year":"2025","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.bbamcr.2010.09.019","article-title":"Metabolic Control of Mitochondrial Biogenesis through the PGC-1 Family Regulatory Network","volume":"1813","author":"Scarpulla","year":"2011","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"ref_82","first-page":"D543","article-title":"The PRIDE Database at 20 Years: 2025 Update","volume":"53","author":"Bandla","year":"2024","journal-title":"Nucleic Acids Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1415\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:17:35Z","timestamp":1786076255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":82,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15151415"],"URL":"https:\/\/doi.org\/10.3390\/cells15151415","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}