| First Author | Ashcroft SP | Year | 2020 |
| Journal | Am J Physiol Cell Physiol | Volume | 318 |
| Issue | 3 | Pages | C536-C541 |
| PubMed ID | 31940245 | Mgi Jnum | J:285317 |
| Mgi Id | MGI:6392421 | Doi | 10.1152/ajpcell.00568.2019 |
| Citation | Ashcroft SP, et al. (2020) The vitamin D receptor regulates mitochondrial function in C2C12 myoblasts. Am J Physiol Cell Physiol 318(3):C536-C541 |
| abstractText | Vitamin D deficiency has been linked to a reduction in skeletal muscle function and oxidative capacity; however, the mechanistic bases of these impairments are poorly understood. The biological actions of vitamin D are carried out via the binding of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) to the vitamin D receptor (VDR). Recent evidence has linked 1alpha,25(OH)2D3 to the regulation of skeletal muscle mitochondrial function in vitro; however, little is known with regard to the role of the VDR in this process. To examine the regulatory role of the VDR in skeletal muscle mitochondrial function, we used lentivirus-mediated shRNA silencing of the VDR in C2C12 myoblasts (VDR-KD) and examined mitochondrial respiration and protein content compared with an shRNA scrambled control. VDR protein content was reduced by ~95% in myoblasts and myotubes (P < 0.001). VDR-KD myoblasts displayed a 30%, 30%, and 36% reduction in basal, coupled, and maximal respiration, respectively (P < 0.05). This phenotype was maintained in VDR-KD myotubes, displaying a 34%, 33%, and 48% reduction in basal, coupled, and maximal respiration (P < 0.05). Furthermore, ATP production derived from oxidative phosphorylation (ATPOx) was reduced by 20%, suggesting intrinsic impairments within the mitochondria following VDR-KD. However, despite the observed functional decrements, mitochondrial protein content, as well as markers of mitochondrial fission were unchanged. In summary, we highlight a direct role for the VDR in regulating skeletal muscle mitochondrial respiration in vitro, providing a potential mechanism as to how vitamin D deficiency might impact upon skeletal muscle oxidative capacity. |
