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The vitamin D receptor regulates mitochondrial function in C2C12 myoblasts.


ABSTRACT: 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 1?,25-dihydroxyvitamin D3 (1?,25(OH)2D3) to the vitamin D receptor (VDR). Recent evidence has linked 1?,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.

SUBMITTER: Ashcroft SP 

PROVIDER: S-EPMC7099523 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The vitamin D receptor regulates mitochondrial function in C2C12 myoblasts.

Ashcroft Stephen P SP   Bass Joseph J JJ   Kazi Abid A AA   Atherton Philip J PJ   Philp Andrew A  

American journal of physiology. Cell physiology 20200115 3


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 1α,25-dihydroxyvitamin D<sub>3</sub> (1α,25(OH)<sub>2</sub>D<sub>3</sub>) to the vitamin D receptor (VDR). Recent evidence has linked 1α,25(OH)<sub>2</sub>D<sub>3</sub> to the regulation of skeletal muscle mitochondrial function in vitro; however, li  ...[more]

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