{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:58:24Z","timestamp":1768345104487,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/00439"],"award-info":[{"award-number":["PI23\/00439"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Plan Propio 2025 of INIBICA","award":["PP25-TECL"],"award-info":[{"award-number":["PP25-TECL"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Preeclampsia is a serious pregnancy disorder of unknown etiology. One of its cellular hallmarks is increased mitochondrial dysfunction in placental tissue. Further investigation into this aspect may help elucidate the molecular basis of preeclampsia. A total of 24 pregnant women who delivered by cesarean section participated in the study: n = 13 controls and n = 11 diagnosed with preeclampsia. Maternal blood samples were collected to assess the biochemical profile, and demographic and clinical data were recorded. Placental trophoblast samples were processed to isolate mitochondria and perform molecular biology assays. Women with preeclampsia exhibited the characteristic clinical features of the disease, along with biochemical alterations consistent with an inflammatory process. A significant decrease (73%) in mitochondrial DNA (mtDNA) copy number in trophoblastic tissue and a reduction in citrate synthase (CS) activity (\u221251%) in cytotrophoblast mitochondria-enriched fractions were observed in preeclampsia, indicating mitochondrial dysfunction accompanied by a loss of functional mitochondrial mass. In addition, we detected a marked decrease in MnSOD levels (\u221232%), together with an increase in the LC3II\/LC3I ratio (47%) in cytotrophoblast mitochondria-enriched fractions, supporting the presence of mitochondrial alterations and suggesting the possible activation of mitophagy specifically in this cell type. Moreover, coenzyme Q10 (CoQ10) levels were elevated by 31% in trophoblastic villi. A pronounced 2.5-fold increase in CoQ10 normalized to CS activity (CoQ10\/CS) was detected specifically in cytotrophoblasts from preeclamptic placentas. Importantly, we did not observe these alterations in the syncytiotrophoblast. In conclusion, preeclampsia is associated with mitochondrial dysfunction and increased CoQ10 levels normalized to CS activity, specifically in cytotrophoblast mitochondria, with findings being consistent with a possible involvement of mitophagy in this cell type. These findings suggest that cytotrophoblast mitochondrial metabolism may be more affected in preeclampsia compared with syncytiotrophoblasts, and that CoQ10 accumulation together with the possible activation of mitophagy may represent cellular defense mechanisms. Due to the limitations of the study, it should be considered exploratory and hypothesis-generating, and its results should be regarded as preliminary.<\/jats:p>","DOI":"10.3390\/biology15020139","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:52:57Z","timestamp":1768319577000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Dysfunction Combined with Elevated CoQ10 Levels Specifically in Placental Cytotrophoblasts Suggests a Role for Mitophagy in Preeclampsia"],"prefix":"10.3390","volume":"15","author":[{"given":"Jessica","family":"\u00c1balos-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Inflammation and Metabolic Syndrome in Pregnancy Group (CO25), Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-0169","authenticated-orcid":false,"given":"Francisco","family":"Visiedo","sequence":"additional","affiliation":[{"name":"Inflammation and Metabolic Syndrome in Pregnancy Group (CO25), Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Department of Human Anatomy and Embryology, University of C\u00e1diz, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-804X","authenticated-orcid":false,"given":"Mar\u00eda Victoria","family":"Cascajo-Almenara","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology, CIBERER, National Institute of Health Carlos III (ISCIII), Pablo de Olavide University-CSIC-JA, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-2466","authenticated-orcid":false,"given":"Celeste","family":"Santos-Rosendo","sequence":"additional","affiliation":[{"name":"Inflammation and Metabolic Syndrome in Pregnancy Group (CO25), Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Department of Biology, University of C\u00e1diz, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Melero-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Inflammation and Metabolic Syndrome in Pregnancy Group (CO25), Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Division of Maternal-Fetal Medicine, Obstetrics and Gynecology Department, Puerta del Mar University Hospital, 11009 C\u00e1diz, Spain"},{"name":"Area of Obstetrics and Gynaecology, Department of Child and Mother Health and Radiology, School of Medicine, University of C\u00e1diz, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2379-796X","authenticated-orcid":false,"given":"Carlos","family":"Santos-Oca\u00f1a","sequence":"additional","affiliation":[{"name":"Andalusian Centre for Developmental Biology, CIBERER, National Institute of Health Carlos III (ISCIII), Pablo de Olavide University-CSIC-JA, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0870-6935","authenticated-orcid":false,"given":"Luis","family":"V\u00e1zquez-Fonseca","sequence":"additional","affiliation":[{"name":"Inflammation and Metabolic Syndrome in Pregnancy Group (CO25), Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Area of Biochemistry and Molecular Biology, Department of Biomedicine, Biotechnology and Public Health, University of C\u00e1diz, 11001 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-6541","authenticated-orcid":false,"given":"Fernando","family":"Bugatto","sequence":"additional","affiliation":[{"name":"Inflammation and Metabolic Syndrome in Pregnancy Group (CO25), Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA), 11009 C\u00e1diz, Spain"},{"name":"Division of Maternal-Fetal Medicine, Obstetrics and Gynecology Department, Puerta del Mar University Hospital, 11009 C\u00e1diz, Spain"},{"name":"Area of Obstetrics and Gynaecology, Department of Child and Mother Health and Radiology, School of Medicine, University of C\u00e1diz, 11009 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fox, R., Kitt, J., Leeson, P., Aye, C.Y.L., and Lewandowski, A.J. (2019). Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101625"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41581-019-0119-6","article-title":"Pre-eclampsia: Pathogenesis, novel diagnostics and therapies","volume":"15","author":"Phipps","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.placenta.2021.05.002","article-title":"Syncytiotrophoblast stress in early onset preeclampsia: The issues perpetuating the syndrome","volume":"113","author":"Chiarello","year":"2021","journal-title":"Placenta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S907","DOI":"10.1016\/j.ajog.2020.09.047","article-title":"Syncytiotrophoblast stress in preeclampsia: The convergence point for multiple pathways","volume":"226","author":"Redman","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1136\/bmj.38555.462685.8F","article-title":"Recurrence of pre-eclampsia across generations: Exploring fetal and maternal genetic components in a population based cohort","volume":"331","author":"Vatten","year":"2005","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"227s","DOI":"10.1083\/jcb.91.3.227s","article-title":"Mitochondria: A historical review","volume":"91","author":"Ernster","year":"1981","journal-title":"J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E981","DOI":"10.1152\/ajpendo.00354.2020","article-title":"Mitochondrial transformations in the aging human placenta","volume":"319","author":"Bartho","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Aouache, R., Biquard, L., Vaiman, D., and Miralles, F. (2018). Oxidative stress in preeclampsia and placental diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051496"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.placenta.2011.11.027","article-title":"Decreased mitochondrial fatty acid oxidation in placentas from women with preeclampsia","volume":"33","author":"Bartha","year":"2012","journal-title":"Placenta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s11906-022-01184-7","article-title":"Mitochondrial Dysfunction in the Pathogenesis of Preeclampsia","volume":"24","author":"Hu","year":"2022","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"165354","DOI":"10.1016\/j.bbadis.2018.12.005","article-title":"Oxidative stress: Normal pregnancy versus preeclampsia","volume":"1866","author":"Chiarello","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6323086","DOI":"10.1155\/2016\/6323086","article-title":"Downregulation of Mitofusin 2 in Placenta Is Related to Preeclampsia","volume":"2016","author":"Yu","year":"2016","journal-title":"Biomed Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20469","DOI":"10.1038\/s41598-021-99837-1","article-title":"Impaired placental mitophagy and oxidative stress are associated with dysregulated BNIP3 in preeclampsia","volume":"11","author":"Zhou","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41419-018-0360-0","article-title":"Ceramide-induced BOK promotes mitochondrial fission in preeclampsia","volume":"9","author":"Ausman","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hidalgo-Guti\u00e9rrez, A., Gonz\u00e1lez-Garc\u00eda, P., D\u00edaz-Casado, M.E., Barriocanal-Casado, E., L\u00f3pez-Herrador, S., Quinzii, C.M., and L\u00f3pez, L.C. (2021). Metabolic targets of coenzyme q10 in mitochondria. Antioxidants, 10.","DOI":"10.3390\/antiox10040520"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/biof.5520250117","article-title":"Coenzyme Q10 is increased in placenta and cord blood during preeclampsia","volume":"25","author":"Teran","year":"2005","journal-title":"BioFactors"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1089\/ars.2014.5936","article-title":"Amniotic Coenzyme Q10: Is It Related to Pregnancy Outcomes?","volume":"21","author":"Giannubilo","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ijgo.2008.11.033","article-title":"Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia","volume":"105","author":"Teran","year":"2009","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/10641955.2019.1649420","article-title":"CoQ10 alleviate preeclampsia symptoms by enhancing the function of mitochondria in the placenta of pregnant rats with preeclampsia","volume":"38","author":"Xu","year":"2019","journal-title":"Hypertens. Pregnancy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.placenta.2019.05.004","article-title":"Mitochondrial isolation, cryopreservation and preliminary biochemical characterisation from placental cytotrophoblast and syncytiotrophoblast","volume":"82","author":"Fisher","year":"2019","journal-title":"Placenta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/nprot.2012.058","article-title":"Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells","volume":"7","author":"Spinazzi","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_23","first-page":"2186","article-title":"Placental Mitochondrial Abnormalities in Preeclampsia","volume":"28","author":"Vangrieken","year":"2021","journal-title":"Reprod. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jahan, F., Vasam, G., Green, A.E., Bainbridge, S.A., and Menzies, K.J. (2023). Placental Mitochondrial Function and Dysfunction in Preeclampsia. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202301.0538.v2"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114063","DOI":"10.1016\/j.biopha.2022.114063","article-title":"The biomedical potential of tardigrade proteins: A review","volume":"158","author":"Kasianchuk","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/cdd.2014.150","article-title":"Oxidative stress and autophagy: The clash between damage and metabolic needs","volume":"22","author":"Filomeni","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1097\/AOG.0000000000000451","article-title":"Clinical Risk Factors for Preeclampsia in the 21st Century","volume":"124","author":"Parry","year":"2014","journal-title":"Obstet. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1189\/jlb.1112603","article-title":"A leading role for the immune system in the pathophysiology of preeclampsia","volume":"94","year":"2013","journal-title":"J. Leukoc. Biol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/2\/139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T16:10:14Z","timestamp":1768320614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/2\/139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biology15020139"],"URL":"https:\/\/doi.org\/10.3390\/biology15020139","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]}}}