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Carbonic anhydrases (<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s) catalyse the conversion of <jats:styled-content style=\"fixed-case\">CO<\/jats:styled-content><jats:sub>2<\/jats:sub> to <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/febs14779-math-0001.png\" xlink:title=\"urn:x-wiley:1742464X:media:febs14779:febs14779-math-0001\"\/> and H<jats:sup>+<\/jats:sup> and are thus essential for this process. Herein, we inhibited <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s with acetazolamide \u2013 <jats:styled-content style=\"fixed-case\">ACT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>\u20100111 \u2013 to study their involvement in the metabolism, mitochondrial potential, mitochondrial biogenesis and lipid metabolism of human Sertoli cells (<jats:styled-content style=\"fixed-case\">hSC<\/jats:styled-content>s), obtained from biopsies from men with conserved spermatogenesis. We were able to identify three isoforms of <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s, one mitochondrial isoform (<jats:styled-content style=\"fixed-case\">CA VB<\/jats:styled-content>) and two cell membrane\u2010bound isoforms (<jats:styled-content style=\"fixed-case\">CA IX<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CA XII<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">hSC<\/jats:styled-content>s. When assessing the expression of markers for mitochondrial biogenesis, we observed a decrease in <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1, <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>1\u03b1 and <jats:styled-content style=\"fixed-case\">NRF<\/jats:styled-content>\u20101 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>s after all <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s were inhibited, resulting in decreased mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> copy numbers. This was followed by an increased production of lactate and alanine in the same conditions. In addition, consumption of glucose was maintained after inhibition of all <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s in <jats:styled-content style=\"fixed-case\">hSC<\/jats:styled-content>s. These results indicate a reduced conversion of pyruvate to acetyl\u2010coA, possibly due to decreased mitochondrial function, caused by <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content> inhibition in <jats:styled-content style=\"fixed-case\">hSC<\/jats:styled-content>s. Inhibition of <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s also caused alterations in lipid metabolism, since we detected an increased expression of hormone\u2010sensitive lipase (<jats:styled-content style=\"fixed-case\">HSL<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">hSC<\/jats:styled-content>s. Our results suggest that <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s are essential for mitochondrial biogenesis, glucose and lipid metabolism in <jats:styled-content style=\"fixed-case\">hSC<\/jats:styled-content>s. This is the first report showing that <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>s play an essential role in <jats:styled-content style=\"fixed-case\">hSC<\/jats:styled-content> metabolic dynamics, being involved in mitochondrial biogenesis and controlling lactate production.<\/jats:p>","DOI":"10.1111\/febs.14779","type":"journal-article","created":{"date-parts":[[2019,2,6]],"date-time":"2019-02-06T13:22:46Z","timestamp":1549459366000},"page":"1393-1406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Carbonic anhydrases are involved in mitochondrial biogenesis and control the production of lactate by human Sertoli cells"],"prefix":"10.1111","volume":"286","author":[{"given":"Raquel L.","family":"Bernardino","sequence":"first","affiliation":[{"name":"Department of Microscopy Laboratory of Cell Biology Institute of Biomedical Sciences Abel Salazar (ICBAS) and Multidisciplinary Unit for 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