{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:55:33Z","timestamp":1768506933321,"version":"3.49.0"},"posted":{"date-parts":[[2023,7,20]]},"group-title":"Biochemistry","reference-count":38,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,7,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Coenzyme Q\n                  <jats:sub>10<\/jats:sub>\n                  (CoQ\n                  <jats:sub>10<\/jats:sub>\n                  ) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson\u2019s disease, and hypertension. Unfortunately, treatment with exogenous oral CoQ\n                  <jats:sub>10<\/jats:sub>\n                  is often ineffective, likely due to the extreme hydrophobicity and high molecular weight of CoQ\n                  <jats:sub>10<\/jats:sub>\n                  . Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ\n                  <jats:sub>10<\/jats:sub>\n                  in human cells. We demonstrate that CoQ\n                  <jats:sub>4<\/jats:sub>\n                  can perform multiple functions of CoQ\n                  <jats:sub>10<\/jats:sub>\n                  in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ\n                  <jats:sub>4<\/jats:sub>\n                  as a supplement for CoQ\n                  <jats:sub>10<\/jats:sub>\n                  deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ\n                  <jats:sub>4<\/jats:sub>\n                  selectively to mitochondria using triphenylphosphonium (TPP). Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ\n                  <jats:sub>4<\/jats:sub>\n                  , laying the groundwork for further development.\n                <\/jats:p>","DOI":"10.1101\/2023.07.20.549963","type":"posted-content","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:34Z","timestamp":1689897634000},"source":"Crossref","is-referenced-by-count":1,"title":["Coenzyme Q\n                  <sub>4<\/sub>\n                  is a functional substitute for coenzyme Q\n                  <sub>10<\/sub>\n                  and can be targeted to the mitochondria"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3635-771X","authenticated-orcid":false,"given":"Laura H.","family":"Steenberge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1601-2538","authenticated-orcid":false,"given":"Andrew Y.","family":"Sung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5326-5358","authenticated-orcid":false,"given":"Jing","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0001-0087","authenticated-orcid":false,"given":"David J.","family":"Pagliarini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023072413100690000_2023.07.20.549963v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2022.12.006"},{"key":"2023072413100690000_2023.07.20.549963v2.2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9749-9"},{"key":"2023072413100690000_2023.07.20.549963v2.3","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535072"},{"key":"2023072413100690000_2023.07.20.549963v2.4","doi-asserted-by":"crossref","first-page":"975","DOI":"10.3390\/jpm12060975","article-title":"Coenzyme Q10 and Parkinsonian Syndromes: A Systematic Review","volume":"12","year":"2022","journal-title":"J Personalized Medicine"},{"key":"2023072413100690000_2023.07.20.549963v2.5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-121214-104412"},{"key":"2023072413100690000_2023.07.20.549963v2.6","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/biof.1733","article-title":"Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging","volume":"47","year":"2021","journal-title":"Biofactors"},{"key":"2023072413100690000_2023.07.20.549963v2.7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2020.03.006","article-title":"Effect of Coenzyme Q10 on statin-associated myalgia and adherence to statin therapy: A systematic review and meta-analysis","volume":"299","year":"2020","journal-title":"Atherosclerosis"},{"key":"2023072413100690000_2023.07.20.549963v2.8","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1111\/jcmm.17488","article-title":"The efficacy of coenzyme Q10 treatment in alleviating the symptoms of primary coenzyme Q10 deficiency: A systematic review","volume":"26","year":"2022","journal-title":"J Cell Mol Med"},{"key":"2023072413100690000_2023.07.20.549963v2.9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10072-016-2757-9","article-title":"The efficacy and safety of coenzyme Q10 in Parkinson\u2019s disease: a meta-analysis of randomized controlled trials","volume":"38","year":"2017","journal-title":"Neurol Sci"},{"key":"2023072413100690000_2023.07.20.549963v2.10","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.nut.2018.05.020","article-title":"Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization","volume":"57","year":"2019","journal-title":"Nutrition"},{"key":"2023072413100690000_2023.07.20.549963v2.11","unstructured":"Zhang, Y. , Aberg, F. , Appelkvist, E.-L. , Dallner, G. , and Ernster, L. 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