RT Journal Article
SR Electronic
T1 The Vitamin D Receptor (VDR) Regulates Mitochondrial Function in C2C12 Myoblasts
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 872127
DO 10.1101/872127
A1 Stephen P. Ashcroft
A1 Joseph J. Bass
A1 Abid A. Kazi
A1 Philip J. Atherton
A1 Andrew Philp
YR 2019
UL http://biorxiv.org/content/early/2019/12/11/872127.abstract
AB Vitamin D deficiency has been linked to a reduction in skeletal muscle function and oxidative capacity, however, the mechanistic basis of these impairments are poorly understood. The biological actions of vitamin D are carried out via the binding of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) to the vitamin D receptor (VDR). Recent evidence has linked 1α,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 utilised lentiviral mediated shRNA silencing of the VDR in C2C12 myoblasts (VDR-KD) and examined mitochondrial respiration and protein content compared to 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 fusion and 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.