{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:30:19Z","timestamp":1776299419938,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T00:00:00Z","timestamp":1593216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-1330803"],"award-info":[{"award-number":["MCB-1330803"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-1712608"],"award-info":[{"award-number":["MCB-1712608"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an important antioxidant present in all cellular membranes. CoQ deficiencies are frequent in aging and in age-related diseases, and current treatments are limited to CoQ supplementation. Strategies that rely on CoQ supplementation suffer from poor uptake and trafficking of this very hydrophobic molecule. In a previous study, the dietary flavonol kaempferol was reported to serve as a CoQ ring precursor and to increase the CoQ content in kidney cells, but neither the part of the molecule entering CoQ biosynthesis nor the mechanism were described. In this study, kaempferol labeled specifically in the B-ring was isolated from Arabidopsis plants. Kidney cells treated with this compound incorporated the B-ring of kaempferol into newly synthesized CoQ, suggesting that the B-ring is metabolized via a mechanism described in plant cells. Kaempferol is a natural flavonoid present in fruits and vegetables and possesses antioxidant, anticancer, and anti-inflammatory therapeutic properties. A better understanding of the role of kaempferol as a CoQ ring precursor makes this bioactive compound a potential candidate for the design of interventions aiming to increase endogenous CoQ biosynthesis and may improve CoQ deficient phenotypes in aging and disease.<\/jats:p>","DOI":"10.3390\/molecules25132955","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T16:06:54Z","timestamp":1593533214000},"page":"2955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Metabolism of the Flavonol Kaempferol in Kidney Cells Liberates the B-ring to Enter Coenzyme Q Biosynthesis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-2700","authenticated-orcid":false,"given":"Luc\u00eda","family":"Fern\u00e1ndez-del-R\u00edo","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2970-3183","authenticated-orcid":false,"given":"Eric","family":"Soubeyrand","sequence":"additional","affiliation":[{"name":"Department of Horticultural Sciences, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-9797","authenticated-orcid":false,"given":"Gilles J.","family":"Basset","sequence":"additional","affiliation":[{"name":"Department of Horticultural Sciences, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6426-3833","authenticated-orcid":false,"given":"Catherine F.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.tem.2019.08.009","article-title":"The complexity of making ubiquinone","volume":"30","author":"Wang","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1042\/EBC20170106","article-title":"Coenzyme Q10 deficiencies: Pathways in yeast and humans","volume":"62","author":"Awad","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_3","first-page":"2240","article-title":"Coenzyme Q10: From bench to clinic in aging diseases, a translational review","volume":"59","author":"Villalba","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bbrc.2010.02.147","article-title":"Coenzyme Q-biosynthesis and functions","volume":"396","author":"Bentinger","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.tibs.2017.06.008","article-title":"Biochemistry of mitochondrial coenzyme Q biosynthesis","volume":"42","author":"Stefely","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Diaz-Casado, M.E., Quiles, J.L., Barriocanal-Casado, E., Gonzalez-Garcia, P., Battino, M., Lopez, L.C., and Varela-Lopez, A. (2019). The paradox of coenzyme Q10 in aging. Nutrients, 11.","DOI":"10.3390\/nu11092221"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1016\/j.mito.2007.02.006","article-title":"The antioxidant role of coenzyme q","volume":"7","author":"Bentinger","year":"2007","journal-title":"Mitochondrion"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Barcelos, I.P., and Haas, R.H. (2019). CoQ10 and aging. Biology (Basel), 8.","DOI":"10.3390\/biology8020028"},{"key":"ref_9","first-page":"1","article-title":"Coenzyme Q10 supplementation in aging and disease","volume":"9","author":"Bernier","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/BF02535072","article-title":"Age-related changes in the lipid compositions of rat and human tissues","volume":"24","author":"Appelkvist","year":"1989","journal-title":"Lipids"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Varela-L\u00f3pez, A., Giampieri, F., Battino, M., and Quiles, J. (2016). Coenzyme Q and its role in the dietary therapy against aging. Molecules, 21.","DOI":"10.3390\/molecules21030373"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.phrs.2017.01.032","article-title":"Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials","volume":"119","author":"Fan","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhai, J., Bo, Y., Lu, Y., Liu, C., and Zhang, L. (2017). Effects of coenzyme Q10 on markers of inflammation: A systematic review and meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170172"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e002639","DOI":"10.1161\/CIRCHEARTFAILURE.115.002639","article-title":"Coenzyme Q10 and heart failure: A state-of-the-art review","volume":"9","author":"Sharma","year":"2016","journal-title":"Circ. Heart Fail."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8930","DOI":"10.1021\/acs.jafc.7b03300","article-title":"Preparation and characterization of mucoadhesive nanoparticles for enhancing cellular uptake of coenzyme Q10","volume":"65","author":"Lee","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","first-page":"133","article-title":"Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization","volume":"57","author":"Navas","year":"2018","journal-title":"Nutrition"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.freeradbiomed.2017.06.006","article-title":"Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor","volume":"110","author":"Nag","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1105\/tpc.18.00688","article-title":"The peroxidative cleavage of kaempferol contributes to the biosynthesis of the benzenoid moiety of ubiquinone in plants","volume":"30","author":"Soubeyrand","year":"2018","journal-title":"Plant. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0014-5793(72)80679-3","article-title":"Enzymatic synthesis of aromatic compounds in higher plants: Formation of naringenin (5,7,4\u2019-trihydroxyflavanone) from p-coumaroyl coenzyme a and malonyl coenzyme a","volume":"28","author":"Kreuzaler","year":"1972","journal-title":"FEBS Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1515\/BC.2000.095","article-title":"Identification of the Arabidopsis thaliana flavonoid 3\u2019-hydroxylase gene and functional expression of the encoded p450 enzyme","volume":"381","author":"Schoenbohm","year":"2000","journal-title":"Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1194\/jlr.M057919","article-title":"Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis","volume":"56","author":"Xie","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"298","DOI":"10.2174\/138955711795305335","article-title":"A review on the dietary flavonoid kaempferol","volume":"11","year":"2011","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2015.05.002","article-title":"Kaempferol and inflammation: From chemistry to medicine","volume":"99","author":"Devi","year":"2015","journal-title":"Pharmacol Res."},{"key":"ref_24","first-page":"2759","article-title":"Recent progress regarding kaempferol for the treatment of various diseases","volume":"18","author":"Ren","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Imran, M., Salehi, B., Sharifi-Rad, J., Aslam Gondal, T., Saeed, F., Imran, A., Shahbaz, M., Tsouh Fokou, P.V., Umair Arshad, M., and Khan, H. (2019). Kaempferol: A key emphasis to its anticancer potential. Molecules, 24.","DOI":"10.3390\/molecules24122277"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/ptr.6227","article-title":"Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review","volume":"33","author":"Imran","year":"2019","journal-title":"Phytother Res."},{"key":"ref_27","first-page":"79","article-title":"Flavonoids--food sources and health benefits","volume":"65","author":"Kozlowska","year":"2014","journal-title":"Rocz. Panstw. Zakl. Hig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.medici.2016.03.003","article-title":"Multiplicity of effects and health benefits of resveratrol","volume":"52","author":"Kursvietiene","year":"2016","journal-title":"Medicina (Kaunas)"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.fitote.2016.10.008","article-title":"Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats","volume":"115","author":"Zabela","year":"2016","journal-title":"Fitoterapia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0378-4347(88)80009-4","article-title":"Determination of coenzyme Q10, alpha-tocopherol and cholesterol in biological samples by coupled-column liquid chromatography with coulometric and ultraviolet detection","volume":"425","author":"Edlund","year":"1988","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"C323","DOI":"10.1152\/ajpcell.1995.269.2.C323","article-title":"Expression and function of p-glycoprotein in a mouse kidney cell line","volume":"269","author":"Ernest","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0076-6879(90)82008-P","article-title":"Quantitation of protein","volume":"182","author":"Stoscheck","year":"1990","journal-title":"Methods Enzymol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/13\/2955\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:43:34Z","timestamp":1760175814000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/13\/2955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,27]]},"references-count":32,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["molecules25132955"],"URL":"https:\/\/doi.org\/10.3390\/molecules25132955","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,27]]}}}