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Carbonic anhydrases are involved in mitochondrial biogenesis and control the production of lactate by human Sertoli cells
Author(s) -
Bernardino Raquel L.,
Dias Tânia R.,
Moreira Bruno P.,
Cunha Mariana,
Barros Alberto,
Oliveira Elsa,
Sousa Mário,
Alves Marco G.,
Oliveira Pedro F.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14779
Subject(s) - mitochondrial biogenesis , biology , mitochondrion , sertoli cell , gene isoform , biochemistry , microbiology and biotechnology , metabolism , lipid metabolism , glycolysis , chemistry , spermatogenesis , endocrinology , gene
The process that allows cells to control their pH and bicarbonate levels is essential for ionic and metabolic equilibrium. Carbonic anhydrases ( CA s) catalyse the conversion of CO 2 to HCO 3 − and H + and are thus essential for this process. Herein, we inhibited CA s with acetazolamide – ACT and SLC ‐0111 – to study their involvement in the metabolism, mitochondrial potential, mitochondrial biogenesis and lipid metabolism of human Sertoli cells ( hSC s), obtained from biopsies from men with conserved spermatogenesis. We were able to identify three isoforms of CA s, one mitochondrial isoform ( CA VB ) and two cell membrane‐bound isoforms ( CA IX and CA XII ) in hSC s. When assessing the expression of markers for mitochondrial biogenesis, we observed a decrease in HIF ‐1α, SIRT 1, PGC 1α and NRF ‐1 mRNA s after all CA s were inhibited, resulting in decreased mitochondrial DNA 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 CA s in hSC s. These results indicate a reduced conversion of pyruvate to acetyl‐coA, possibly due to decreased mitochondrial function, caused by CA inhibition in hSC s. Inhibition of CA s also caused alterations in lipid metabolism, since we detected an increased expression of hormone‐sensitive lipase ( HSL ) in hSC s. Our results suggest that CA s are essential for mitochondrial biogenesis, glucose and lipid metabolism in hSC s. This is the first report showing that CA s play an essential role in hSC metabolic dynamics, being involved in mitochondrial biogenesis and controlling lactate production.