The vitamin D receptor regulates mitochondrial function in C2C12 myoblasts

Area of Science:

• Biochemistry
• Cell Biology
• Muscle Physiology

Background:

• Vitamin D deficiency is associated with reduced skeletal muscle function and oxidative capacity.
• The mechanisms underlying these impairments are not fully understood.
• The vitamin D receptor (VDR) mediates the biological actions of vitamin D, but its role in skeletal muscle mitochondria is unclear.

Purpose of the Study:

• To investigate the regulatory role of the VDR in skeletal muscle mitochondrial function.
• To examine the impact of VDR deficiency on mitochondrial respiration and ATP production in C2C12 myoblasts and myotubes.

Main Methods:

• Lentivirus-mediated shRNA silencing was used to reduce VDR expression in C2C12 myoblasts (VDR-KD).
• Mitochondrial respiration (basal, coupled, maximal) and ATP production were measured in VDR-KD and control cells.
• Mitochondrial protein content and markers of mitochondrial fission were assessed.

Main Results:

• VDR protein content was significantly reduced (~95%) in VDR-KD myoblasts and myotubes.
• VDR-KD cells exhibited marked reductions in basal, coupled, and maximal mitochondrial respiration (30-48%).
• ATP production from oxidative phosphorylation was reduced by 20% in VDR-KD cells, despite unchanged mitochondrial protein content and fission markers.

Conclusions:

• The VDR plays a direct role in regulating skeletal muscle mitochondrial respiration in vitro.
• VDR deficiency leads to intrinsic mitochondrial impairments affecting oxidative capacity.
• This study provides a potential mechanism linking vitamin D deficiency to reduced skeletal muscle oxidative capacity.