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Mutations affecting\n                    <jats:italic>POLG<\/jats:italic>\n                    are the most prevalent cause of mitochondrial disease because of defective mtDNA replication and lead to a wide spectrum of clinical phenotypes characterized by mtDNA deletions or depletion. Enhancing mitochondrial deoxyribonucleoside triphosphate (dNTP) synthesis effectively rescues mtDNA depletion in different models of defective mtDNA maintenance due to dNTP insufficiency. In this study, we studied mtDNA copy number recovery rates following ethidium bromide\u2010forced depletion in quiescent fibroblasts from patients harboring mutations in different domains of POLG. Whereas control cells spontaneously recovered initial mtDNA levels, POLG\u2010deficient cells experienced a more severe depletion and could not repopulate mtDNA. However, activation of deoxyribonucleoside (dN) salvage by supplementation with dNs plus\n                    <jats:italic>erythro<\/jats:italic>\n                    \u20109\u2010(2\u2010hydroxy\u20103\u2010nonyl) adenine (inhibitor of deoxyadenosine degradation) led to increased mitochondrial dNTP pools and promoted mtDNA repopulation in all tested POLG\u2010mutant cells independently of their specific genetic defect. The treatment did not compromise POLG fidelity because no increase in multiple deletions or point mutations was detected. Our study suggests that physiologic dNTP concentration limits the mtDNA replication rate. We thus propose that increasing mitochondrial dNTP availability could be of therapeutic interest for POLG deficiency and other conditions in which mtDNA maintenance is challenged.\u2014Bl\u00e1zquez\u2010Bermejo, C., Carre\u00f1o\u2010Gago, L., Molina\u2010Granada, D., Aguirre, J., Ramon, J., Torres\u2010Torronteras, J., Cabrera\u2010P\u00e9rez, R., Mart\u00edn, M. \u00c1., Dom\u00ednguez\u2010Gonz\u00e1lez, C., de la Cruz, X., Lomb\u00e8s, A., Garc\u00eda\u2010Arum\u00ed, E., Mart\u00ed, R., C\u00e1mara, Y. Increased dNTP pools rescue mtDNA depletion in human POLG\u2010deficient fibroblasts. FASEB J. 33, 7168\u20137179 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801591r","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T13:57:11Z","timestamp":1552053431000},"page":"7168-7179","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Increased dNTP pools rescue mtDNA depletion in human POLG\u2010deficient fibroblasts"],"prefix":"10.1096","volume":"33","author":[{"given":"Cora","family":"Bl\u00e1zquez-Bermejo","sequence":"first","affiliation":[{"name":"Research Group on Neuromuscular and Mitochondrial Disorders Vail d'Hebron Institut de Recerca Universitat Aut\u00f2noma de Barcelona Barcelona Spain"},{"name":"Biomedical Network Research Centre on Rare Diseases (CIBERER) Instituto de Salud Carlos III Madrid 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