Changes in intracellular energy transfer enzymes in muscles of mice with deleted wolframin (wfs1) gene

Introduction To study the mechanisms of Wolfram syndrome, we assessed the changes in activities, amounts and functional coupling between mitochondria and enzymes involved in the transport of energy in muscles of wfs1‐deficient mice, models of this syndrome. Materials and methods Samples of heart, m. soleus and m. rectus femoris of wfs1‐deficient and wild‐type mice. Real‐time PCR method, spectrophotometry and nano‐LC‐MS/MS analysis of homogenates. Coupling between mitochondria and enzymes was assayed by oxygraphy of permeabilized muscle fibres. Results Compared with wild type, in m. rectus femoris of wfs1‐deficient mice mRNA level of muscle‐type creatine kinase isoform was two times (P<0.05) lower, total activities of creatine and adenylate kinase decreased by 34% (P<0.01) and 48% (P<0.02) respectively. In wfs1‐deficient mice functional coupling of adenylate kinase and mitochondria in heart decreased by 39% (P<0.05), but in m. soleus and m. rectus femoris did not change. Coupling of mitochondria and creatine kinase did not alter in any muscle of wfs1‐deficient mice. The amounts of mitochondrial sarcomeric creatine kinase in wfs1‐deficient m. rectus femoris increased 3.16‐fold (P<0.001) and mitochondrial adenylate kinase 2 2.09‐fold (P<0.01), cytoplasmatic adenylate kinase 1 but 2.12‐fold (P