Changes in glycolytic network and mitochondrial design in creatine kinase-deficient muscles

Skeletal muscles respond with high plasticity to pathobiological conditions or changes in physiological demand by remodeling cytoarchitectural and met abolic characteristics of individual myocytes. We have previously shown tha t muscles of mice without mitochondrial and/or cytosolic creatine kinases ( ScCKmit(-/-) and/or M-CK-/-) partly compensate for the defect(s) by redirec ting metabolic pathways and ultrastructural characteristics. Here, we show by semiquantitative Western blot analysis that the compensatory changes inv olve mutation- and fiber-type-specific coordinated regulation of divergent but functionally coupled groups of proteins. Fast-twitch gastrocnemius musc le of CK-/- mice display a two- to fourfold upregulation of mitochondrial c ytochrome c oxidase, inorganic phosphate carrier, adenine nucleotide transl ocator, and voltage-dependent anion channel proteins. In parallel, cytosoli c myoglobin is upregulated. Slow-twitch soleus muscle responds with changes in the glycolytic enzyme pattern, including a shift in lactate dehydrogena se isoenzyme composition. Adaptations in the network for oxidative adenosin e triphosphate (ATP) production are already apparent at 17 days of age. (C) 2001 John Wiley & Sons, Inc.