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Considering that CoQ<jats:sub>10<\/jats:sub> synthesis and most of its functions are carried out in mitochondria, CoQ<jats:sub>10<\/jats:sub> deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ<jats:sub>10<\/jats:sub> deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ<jats:sub>10<\/jats:sub> supplementation. Defects in components of the synthesis machinery caused by mutations in <jats:italic>COQ<\/jats:italic> genes generate the primary deficiency of CoQ<jats:sub>10<\/jats:sub>. Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ<jats:sub>10<\/jats:sub> deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ<jats:sub>10<\/jats:sub> deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ<jats:sub>10<\/jats:sub> deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ<jats:sub>10<\/jats:sub> deficiencies. Further, a more in\u2010depth analysis of CoQ<jats:sub>10<\/jats:sub> secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency.<\/jats:p>","DOI":"10.1002\/biof.1733","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T15:58:36Z","timestamp":1619020716000},"page":"551-569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Secondary <scp>CoQ<sub>10<\/sub><\/scp> deficiency, bioenergetics unbalance in disease and aging"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-7966","authenticated-orcid":false,"given":"Pl\u00e1cido","family":"Navas","sequence":"first","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-804X","authenticated-orcid":false,"given":"Mar\u00eda V.","family":"Cascajo","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3688-2143","authenticated-orcid":false,"given":"Mar\u00eda","family":"Alc\u00e1zar\u2010Fabra","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-6726","authenticated-orcid":false,"given":"Juan D.","family":"Hern\u00e1ndez\u2010Camacho","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-8254","authenticated-orcid":false,"given":"Ana","family":"S\u00e1nchez\u2010Cuesta","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0675-6485","authenticated-orcid":false,"given":"Ana Bel\u00e9n Cort\u00e9s","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"},{"name":"Laboratorio de Fisiopatolog\u00eda Celular y Bioenerg\u00e9tica Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-5221","authenticated-orcid":false,"given":"Manuel","family":"Ballesteros\u2010Simarro","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9805-7854","authenticated-orcid":false,"given":"Antonio","family":"Arroyo\u2010Luque","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-4128","authenticated-orcid":false,"given":"Juan Carlos","family":"Rodr\u00edguez\u2010Aguilera","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"},{"name":"CIBERER, Instituto de Salud Carlos III  Madrid Spain"},{"name":"Laboratorio de Fisiopatolog\u00eda Celular y Bioenerg\u00e9tica Universidad Pablo de Olavide\u2010CSIC\u2010JA  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8176-1431","authenticated-orcid":false,"given":"Daniel J. 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