Henzi, Thomas Schwaller, Beat 2015-11-05 Parvalbumin (PV) is a cytosolic Ca²⁺-binding protein acting as a slow-onset Ca²⁺ buffer modulating the shape of Ca²⁺ transients in fast-twitch muscles and a subpopulation of neurons. PV is also expressed in non-excitable cells including distal convoluted tubule (DCT) cells of the kidney, where it might act as an intracellular Ca²⁺ shuttle facilitating transcellular Ca²⁺ resorption. In excitable cells, upregulation of mitochondria in “PV-ergic” cells in PV-/- mice appears to be a general hallmark, evidenced in fast-twitch muscles and cerebellar Purkinje cells. Using Gene Chip Arrays and qRT-PCR, we identified differentially expressed genes in the DCT of PV-/- mice. With a focus on genes implicated in mitochondrial Ca²⁺ transport and membrane potential, uncoupling protein 2 (<em>Ucp2</em>), mitocalcin (<em>Efhd1</em>), mitochondrial calcium uptake 1 (<em>Micu1</em>), mitochondrial calcium uniporter (<em>Mcu</em>), mitochondrial calcium uniporter regulator 1 (<em>Mcur1</em>), cytochrome c oxidase subunit 1 (<em>COX1</em>), and ATP synthase subunit β (<em>Atp5b</em>) were found to be up-upregulated. At the protein level, COX1 was increased by 31 ± 7%, while ATP-synthase subunit β was unchanged. This suggested that these mitochondria were better suited to uphold the electrochemical potential across the mitochondrial membrane, necessary for mitochondrial Ca²⁺ uptake. Ectopic expression of PV in PV-negative Madin-Darby canine kidney (MDCK) cells decreased COX1 and concomitantly mitochondrial volume, while ATP synthase subunit β levels remained unaffected. Suppression of PV by shRNA in PV-expressing MDCK cells led subsequently to an increase in COX1 expression. The collapsing of the mitochondrial membrane potential by the uncoupler CCCP occurred at lower concentrations in PV-expressing MDCK cells than in control cells. In support, a reduction of the relative mitochondrial mass was observed in PV-expressing MDCK cells. Deregulation of the cytoplasmic Ca²⁺ buffer PV in kidney cells was counterbalanced <em>in vivo</em> and <em>in vitro</em> by adjusting the relative mitochondrial volume and modifying the mitochondrial protein composition conceivably to increase their Ca²⁺-buffering/sequestration capacity. application/pdf https://folia.unifr.ch/global/documents/304733 https://folia.unifr.ch/documents/304733/files/sch_arp.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0142005 info:eu-repo/semantics/openAccess License undefined PLoS ONE. - 2015, vol. 10, no. 11, p. e0142005 info:eu-repo/classification/udc/57 Antagonistic regulation of parvalbumin expression and mitochondrial calcium handling capacity in renal epithelial cells http://purl.org/coar/resource_type/c_6501