{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T22:29:57Z","timestamp":1761172197654,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018818","name":"National Research Fund","doi-asserted-by":"publisher","award":["K134285","PD142943","FK142971","PC-II-12\/2022"],"award-info":[{"award-number":["K134285","PD142943","FK142971","PC-II-12\/2022"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EK\u00d6P-25 university research scholarship program of the ministry for culture and innovation","award":["EK\u00d6P-25-3-II-ELTE-616"],"award-info":[{"award-number":["EK\u00d6P-25-3-II-ELTE-616"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences"},{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Office","doi-asserted-by":"publisher","award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Council of Scientific and Industrial Research (CSIR) and CSIR-Central Drug Research Institute"},{"name":"Pheo Para Cancer Charity"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pheochromocytomas and paragangliomas (PPGL) are classified as rare cancers but can be highly metastatic, particularly in individuals with inherited succinate dehydrogenase B (SDHB) mutations. As current therapies and the availability of SDHB-deficient animal models are both limited, we have previously constructed a nematode PPGL model, a transgenic worm carrying the R244H missense mutation equivalent to human R230H in the sdhb-1 gene. In this study, we show that R244H mutants display characteristics of PPGL tumors, such as pseudohypoxia activation and the accumulation of reactive oxygen species. The latter can be the result of compromised antioxidant machinery, as R244H mutants have reduced levels of cytosolic and mitochondrial superoxide dismutase enzymes. In addition, the expression of mitophagy markers pink-1 (PTEN-induced putative kinase) and pdr-1 (E3 ubiquitin-protein ligase parkin) were downregulated in R244H mutants, suggesting impaired mitophagy and reflecting the crucial role of mitochondrial health in PPGL pathology. Treatments by the SDH inhibitor fluopyram revealed that the SDH complex carrying the R244H mutation in subunit B displayed residual SDH activity, which was also confirmed by our structural analyses. We also observed a link between dopaminergic neuronal health and SDHB-1.<\/jats:p>","DOI":"10.3390\/ijms262010185","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:44:10Z","timestamp":1760957050000},"page":"10185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Caenorhabditis elegans sdhb-1(R244H) Model Shows Characteristics of Human PPGL Tumor Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Fanni","family":"\u0150sz","sequence":"first","affiliation":[{"name":"Department of Biological Anthropology, E\u00f6tv\u00f6s Lorand University, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmood","family":"Akbar","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"},{"name":"Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow 226031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs Zolt\u00e1n","family":"Zsid\u00f3","sequence":"additional","affiliation":[{"name":"Pharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8013-971X","authenticated-orcid":false,"given":"Csaba","family":"Het\u00e9nyi","sequence":"additional","affiliation":[{"name":"Pharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-3428","authenticated-orcid":false,"given":"Tam\u00e1s I.","family":"Orb\u00e1n","sequence":"additional","affiliation":[{"name":"Gene Regulation Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary"},{"name":"Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7398-9700","authenticated-orcid":false,"given":"\u00c1bel","family":"F\u00f3thi","sequence":"additional","affiliation":[{"name":"Gene Regulation Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary"},{"name":"Department of Molecular Biology, Semmelweis University, H-1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor M.","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Plant Anatomy, E\u00f6tv\u00f6s Lorand University, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-7978","authenticated-orcid":false,"given":"Alexandra","family":"Pintye","sequence":"additional","affiliation":[{"name":"Department of Plant Anatomy, E\u00f6tv\u00f6s Lorand University, H-1117 Budapest, Hungary"},{"name":"Centre for Agricultural Research, Plant Protection Institute, HUN-REN, H-1116 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1811-8595","authenticated-orcid":false,"given":"Attila","family":"Boda","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell and Developmental Biology, E\u00f6tv\u00f6s Lorand University, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-8251","authenticated-orcid":false,"given":"Aamir","family":"Nazir","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"},{"name":"Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow 226031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsolt","family":"Farkas","sequence":"additional","affiliation":[{"name":"Department of Biological Anthropology, E\u00f6tv\u00f6s Lorand University, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-0363","authenticated-orcid":false,"given":"Krisztina","family":"Tak\u00e1cs-Vellai","sequence":"additional","affiliation":[{"name":"Department of Biological Anthropology, E\u00f6tv\u00f6s Lorand University, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E398","DOI":"10.1503\/cmaj.160771","article-title":"Principles of Diagnosis and Management of Neuroendocrine Tumours","volume":"189","author":"Raphael","year":"2017","journal-title":"CMAJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jcp-2023-209060","article-title":"The Road Ahead: A Brief Guide to Navigating the 2022 WHO Classification of Endocrine and Neuroendocrine Tumours","volume":"78","author":"Juhlin","year":"2024","journal-title":"J. Clin. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e756s","DOI":"10.6061\/clinics\/2018\/e756s","article-title":"V Primary Malignant Tumors of the Adrenal Glands","volume":"73","author":"Almeida","year":"2018","journal-title":"Clinics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrc3648","article-title":"Pheochromocytoma and Paraganglioma Pathogenesis: Learning from Genetic Heterogeneity","volume":"14","author":"Dahia","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8812","DOI":"10.1200\/JCO.2005.03.1484","article-title":"Genetic Testing in Pheochromocytoma or Functional Paraganglioma","volume":"23","author":"Amar","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1210\/jc.2006-2315","article-title":"Clinical Presentations, Biochemical Phenotypes, and Genotype-Phenotype Correlations in Patients with Succinate Dehydrogenase Subunit B-Associated Pheochromocytomas and Paragangliomas","volume":"92","author":"Timmers","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s10555-021-10009-z","article-title":"Model Systems in SDHx-Related Pheochromocytoma\/Paraganglioma","volume":"40","author":"Farkas","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"dmm044925","DOI":"10.1242\/dmm.044925","article-title":"The SDHB Arg230His Mutation Causing Familial Paraganglioma Alters Glycolysis in a New Caenorhabditis Elegans Model","volume":"13","author":"Hujber","year":"2020","journal-title":"Dis. Model. Mech."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2967\/jnumed.114.137034","article-title":"Correlation Between In Vivo 18F-FDG PET and Immunohistochemical Markers of Glucose Uptake and Metabolism in Pheochromocytoma and Paraganglioma","volume":"55","author":"Rao","year":"2014","journal-title":"J. Nucl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fliedner, S.M.J., Kaludercic, N., Jiang, X.-S., Hansikova, H., Hajkova, Z., Sladkova, J., Limpuangthip, A., Backlund, P.S., Wesley, R., and Martiniova, L. (2012). Warburg Effect\u2019s Manifestation in Aggressive Pheochromocytomas and Paragangliomas: Insights from a Mouse Cell Model Applied to Human Tumor Tissue. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040949"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2004.11.022","article-title":"Succinate Links TCA Cycle Dysfunction to Oncogenesis by Inhibiting HIF-Alpha Prolyl Hydroxylase","volume":"7","author":"Selak","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bayley, J.-P., and Devilee, P. (2022). Hypothesis: Why Different Types of SDH Gene Variants Cause Divergent Tumor Phenotypes. Genes, 13.","DOI":"10.3390\/genes13061025"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1530\/ERC-15-0099","article-title":"Structural and Functional Consequences of Succinate Dehydrogenase Subunit B Mutations","volume":"22","author":"Kim","year":"2015","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20580","DOI":"10.1074\/jbc.M501894200","article-title":"Roles of the HIF-1 Hypoxia-Inducible Factor During Hypoxia Response in Caenorhabditis Elegans","volume":"280","author":"Shen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7916","DOI":"10.1073\/pnas.141234698","article-title":"The Caenorhabditis Elegans Hif-1 Gene Encodes a BHLH-PAS Protein That Is Required for Adaptation to Hypoxia","volume":"98","author":"Jiang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.tem.2010.02.006","article-title":"Hypoxia Signaling and Resistance in C. Elegans","volume":"21","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1158\/0008-5472.CAN-19-1407","article-title":"Unshielding Multidrug Resistant Cancer Through Selective Iron Depletion of P-Glycoprotein-Expressing Cells","volume":"80","author":"Cserepes","year":"2020","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.neuron.2011.12.037","article-title":"CYSL-1 Interacts with the O2-Sensing Hydroxylase EGL-9 to Promote H2S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans","volume":"73","author":"Ma","year":"2012","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canlet.2019.03.020","article-title":"Reactive Oxygen Species and Cancer: A Complex Interaction","volume":"452","author":"Saikolappan","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11864-020-00787-z","article-title":"Emerging Treatments for Advanced\/Metastatic Pheochromocytoma and Paraganglioma","volume":"21","author":"Ilanchezhian","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1007\/s11064-015-1738-3","article-title":"Loss of SDHB Elevates Catecholamine Synthesis and Secretion Depending on ROS Production and HIF Stabilization","volume":"41","author":"Saito","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1158\/0008-5472.203.65.1","article-title":"A Mutation in the SDHC Gene of Complex II Increases Oxidative Stress, Resulting in Apoptosis and Tumorigenesis","volume":"65","author":"Ishii","year":"2005","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1093\/hmg\/ddp102","article-title":"Functional Study in a Yeast Model of a Novel Succinate Dehydrogenase Subunit B Gene Germline Missense Mutation (C191Y) Diagnosed in a Patient Affected by a Glomus Tumor","volume":"18","author":"Goffrini","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1093\/hmg\/ddm275","article-title":"Succinate Inhibition of Alpha-Ketoglutarate-Dependent Enzymes in a Yeast Model of Paraganglioma","volume":"16","author":"Smith","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7615","DOI":"10.1158\/0008-5472.CAN-06-0833","article-title":"Mutation of Succinate Dehydrogenase Subunit C Results in Increased O2\u00b7\u2212, Oxidative Stress, and Genomic Instability","volume":"66","author":"Slane","year":"2006","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ha, N.M., Tran, S.H., Shim, Y.-H., and Kang, K. (2022). Caenorhabditis Elegans as a Powerful Tool in Natural Product Bioactivity Research. Appl. Biol. Chem., 65.","DOI":"10.1186\/s13765-022-00685-y"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/S0891-5849(03)00142-4","article-title":"Superoxide Reacts with Hydroethidine but Forms a Fluorescent Product That Is Distinctly Different from Ethidium: Potential Implications in Intracellular Fluorescence Detection of Superoxide","volume":"34","author":"Zhao","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Min, H., Youn, E., Kim, J., Son, S.Y., Lee, C.H., and Shim, Y.-H. (2020). Effects of Phosphoethanolamine Supplementation on Mitochondrial Activity and Lipogenesis in a Caffeine Ingestion Caenorhabditis Elegans Model. Nutrients, 12.","DOI":"10.3390\/nu12113348"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14804","DOI":"10.1074\/jbc.M117.788901","article-title":"Hydrogen Peroxide Produced by Superoxide Dismutase SOD-2 Activates Sperm in Caenorhabditis Elegans","volume":"292","author":"Sakamoto","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109203","DOI":"10.1016\/j.celrep.2021.109203","article-title":"PINK1 and Parkin Shape the Organism-Wide Distribution of a Deleterious Mitochondrial Genome","volume":"35","author":"Ahier","year":"2021","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Schleker, A.S.S., Rist, M., Matera, C., Damijonaitis, A., Collienne, U., Matsuoka, K., Habash, S.S., Twelker, K., Gutbrod, O., and Saalw\u00e4chter, C. (2022). Mode of Action of Fluopyram in Plant-Parasitic Nematodes. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-15782-7"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4161\/cib.20978","article-title":"Conserved Role of Dopamine in the Modulation of Behavior","volume":"5","year":"2012","journal-title":"Commun. Integr. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.bbrc.2011.08.092","article-title":"Sir-2.1 Modulates \u201ccalorie-Restriction-Mediated\u201d Prevention of Neurodegeneration in Caenorhabditis Elegans: Implications for Parkinson\u2019s Disease","volume":"413","author":"Jadiya","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.taap.2011.07.021","article-title":"Dopaminergic Neurotoxicant 6-OHDA Induces Oxidative Damage Through Proteolytic Activation of PKC\u03b4 in Cell Culture and Animal Models of Parkinson\u2019s Disease","volume":"256","author":"Latchoumycandane","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s00018-024-05179-2","article-title":"Functional Implications of NHR-210 Enrichment in C. Elegans Cephalic Sheath Glia: Insights into Metabolic and Mitochondrial Disruptions in Parkinson\u2019s Disease Models","volume":"81","author":"Hameed","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6168","DOI":"10.1038\/s41467-022-33849-x","article-title":"The Hypoxia Response Pathway Promotes PEP Carboxykinase and Gluconeogenesis in C. elegans","volume":"13","author":"Vora","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.trecan.2021.10.004","article-title":"Revisiting the HIF Switch in the Tumor and Its Immune Microenvironment","volume":"8","author":"Cowman","year":"2022","journal-title":"Trends Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108219","DOI":"10.1016\/j.envint.2023.108219","article-title":"SDHi Fungicides: An Example of Mitotoxic Pesticides Targeting the Succinate Dehydrogenase Complex","volume":"180","author":"Debizet","year":"2023","journal-title":"Environ. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2169\/internalmedicine.9242-17","article-title":"A Rare Coexistence of Pheochromocytoma and Parkinson\u2019s Disease with Diagnostic Challenges","volume":"57","author":"Sekiya","year":"2018","journal-title":"Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nrneurol.2009.55","article-title":"Diagnosis of Pheochromocytoma in the Setting of Parkinson Disease","volume":"5","author":"Mehta","year":"2009","journal-title":"Nat. Rev. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-4159.2009.06443.x","article-title":"Hypoxia-Inducible Factor 1: A New Hope to Counteract Neurodegeneration?","volume":"112","author":"Correia","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.mito.2017.12.002","article-title":"Succinate Dehydrogenase: Prospect for Neurodegenerative Diseases","volume":"42","year":"2018","journal-title":"Mitochondrion"},{"key":"ref_43","first-page":"247","article-title":"C. elegans in High-Throughput Drug Discovery","volume":"69\u201370","author":"Luke","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The Genetics of Caenorhabditis Elegans","volume":"77","author":"Brenner","year":"1974","journal-title":"Genetics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1038\/s41467-021-24634-3","article-title":"Dietary Thiols Accelerate Aging of C. elegans","volume":"12","author":"Gusarov","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Min, H., Lee, M., Cho, K.S., Lim, H.J., and Shim, Y.-H. (2021). Nicotinamide Supplementation Improves Oocyte Quality and Offspring Development by Modulating Mitochondrial Function in an Aged Caenorhabditis Elegans Model. Antioxidants, 10.","DOI":"10.3390\/antiox10040519"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hoogewijs, D., Houthoofd, K., Matthijssens, F., Vandesompele, J., and Vanfleteren, J.R. (2008). Selection and Validation of a Set of Reliable Reference Genes for Quantitative Sod Gene Expression Analysis in C. Elegans. BMC Mol. Biol., 9.","DOI":"10.1186\/1471-2199-9-9"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.mex.2015.02.002","article-title":"Rapid RNA Analysis of Individual Caenorhabditis Elegans","volume":"2","author":"Ly","year":"2015","journal-title":"MethodsX"},{"key":"ref_49","unstructured":"(2024, January 08). Schr\u00f6dinger Schr\u00f6dinger Release 2024-1: Maestro 2024. Available online: https:\/\/www.schrodinger.com\/life-science\/download\/release-notes\/release-2024-1\/."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15287","DOI":"10.3390\/ijms160715287","article-title":"Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria","volume":"16","author":"Inaoka","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"UniProt Consortium (2019). UniProt: A Worldwide Hub of Protein Knowledge. Nucleic Acids Res., 47, D506\u2013D515.","DOI":"10.1093\/nar\/gky1049"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of Biomolecular Interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/jcc.21922","article-title":"Quantum Mechanically Derived AMBER-Compatible Heme Parameters for Various States of the Cytochrome P450 Catalytic Cycle","volume":"33","author":"Shahrokh","year":"2012","journal-title":"J. Comput. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zsid\u00f3, B.Z., Balog, M., Er\u0151s, N., Po\u00f3r, M., Mohos, V., Flisz\u00e1r-Ny\u00fal, E., Het\u00e9nyi, C., Nagane, M., Hideg, K., and K\u00e1lai, T. (2020). Synthesis of Spin-Labelled Bergamottin: A Potent CYP3A4 Inhibitor with Antiproliferative Activity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020508"},{"key":"ref_57","unstructured":"Stewart, J.J.P., Klamt, A., Thiel, W., Danovich, D., Rocha, G.B., Gieseking, R.L., Moussa, J.E., Kurtz, H.A., Korambath, P., and Merz, K.M. (2022). MOPAC (22.0.0) 2022, Molecular Sciences Software Institute (MolSSI)."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00894-012-1667-x","article-title":"Optimization of Parameters for Semiempirical Methods VI: More Modifications to the NDDO Approximations and Re-Optimization of Parameters","volume":"19","author":"Stewart","year":"2013","journal-title":"J. Mol. Model."},{"key":"ref_59","unstructured":"DeLano, W.L. The PyMOL Molecular Graphics System, Version 2.0 2017."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, Flexible, and Free","volume":"26","author":"Lindahl","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and Testing of a General Amber Force Field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1016\/0040-4020(80)80168-2","article-title":"Iterative Partial Equalization of Orbital Electronegativity\u2014A Rapid Access to Atomic Charges","volume":"36","author":"Gasteiger","year":"1980","journal-title":"Tetrahedron"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1021\/acs.jcim.1c00488","article-title":"Determination of Ligand Binding Modes in Hydrated Viral Ion Channels to Foster Drug Design and Repositioning","volume":"61","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"135761","DOI":"10.1016\/j.molstruc.2023.135761","article-title":"Serum Albumin Binding Studies on Antiproliferative Cyclic C5-Curcuminoid Derivatives Using Spectroscopic Methods and Molecular Modelling","volume":"1287","author":"Tyukodi","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lemli, B., Vilm\u00e1nyi, P., Flisz\u00e1r-Ny\u00fal, E., Zsid\u00f3, B.Z., Het\u00e9nyi, C., Szente, L., and Po\u00f3r, M. (2022). Testing Serum Albumins and Cyclodextrins as Potential Binders of the Mycotoxin Metabolites Alternariol-3-Sulfate, Alternariol-9-Monomethylether and Alternariol-9-Monomethylether-3-Sulfate. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214353"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T04:36:24Z","timestamp":1761107784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":66,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010185"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010185","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,10,20]]}}}