{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:58:03Z","timestamp":1783526283228,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,24]],"date-time":"2021-01-24T00:00:00Z","timestamp":1611446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BBSRC BB\/L010410\/1 and BB\/S009027\/1"],"award-info":[{"award-number":["BBSRC BB\/L010410\/1 and BB\/S009027\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Coenzyme A (CoA) is an essential cofactor present in all living cells. Under physiological conditions, CoA mainly functions to generate metabolically active CoA thioesters, which are indispensable for cellular metabolism, the regulation of gene expression, and the biosynthesis of neurotransmitters. When cells are exposed to oxidative or metabolic stress, CoA acts as an important cellular antioxidant that protects protein thiols from overoxidation, and this function is mediated by protein CoAlation. CoA and its derivatives are strictly maintained at levels controlled by nutrients, hormones, metabolites, and cellular stresses. Dysregulation of their biosynthesis and homeostasis has deleterious consequences and has been noted in a range of pathological conditions, including cancer, diabetes, Reye\u2019s syndrome, cardiac hypertrophy, and neurodegeneration. The biochemistry of CoA biosynthesis, which involves five enzymatic steps, has been extensively studied. However, the existence of a CoA biosynthetic complex and the mode of its regulation in mammalian cells are unknown. In this study, we report the assembly of all five enzymes that drive CoA biosynthesis, in HEK293\/Pank1\u03b2 and A549 cells, using the in situ proximity ligation assay. Furthermore, we show that the association of CoA biosynthetic enzymes is strongly upregulated in response to serum starvation and oxidative stress, whereas insulin and growth factor signaling downregulate their assembly.<\/jats:p>","DOI":"10.3390\/ijms22031131","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T02:07:00Z","timestamp":1611540420000},"page":"1131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Jovana","family":"Bakovi\u0107","sequence":"first","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"L\u00f3pez Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6936-5911","authenticated-orcid":false,"given":"Savvas","family":"Nikolaou","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4619-2226","authenticated-orcid":false,"given":"Bess Yi Kun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3679-7376","authenticated-orcid":false,"given":"Maria-Armineh","family":"Tossounian","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugo","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9425-8624","authenticated-orcid":false,"given":"Christopher","family":"Thrasivoulou","sequence":"additional","affiliation":[{"name":"Research Department of Cell and Developmental Biology, The Centre for Cell and Molecular Dynamics, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriy","family":"Filonenko","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03680 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Gout","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"},{"name":"Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03680 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.plipres.2005.04.001","article-title":"Coenzyme A: Back in action","volume":"44","author":"Leonardi","year":"2005","journal-title":"Prog. 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