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 metabolic characteristics of individual myocytes. We have previously shown that muscles of mice without mitochondrial and/or cytosolic creatine kinases (ScCKmit(-/-) and/or M-CK(-/-)) partly compensate for the defect(s) by redirecting metabolic pathways and ultrastructural characteristics. Here, we show by semiquantitative Western blot analysis that the compensatory changes involve mutation- and fiber-type-specific coordinated regulation of divergent but functionally coupled groups of proteins. Fast-twitch gastrocnemius muscle of CK(--/--) mice display a two- to fourfold upregulation of mitochondrial cytochrome c oxidase, inorganic phosphate carrier, adenine nucleotide translocator, and voltage-dependent anion channel proteins. In parallel, cytosolic myoglobin is upregulated. Slow-twitch soleus muscle responds with changes in the glycolytic enzyme pattern, including a shift in lactate dehydrogenase isoenzyme composition. Adaptations in the network for oxidative adenosine triphosphate (ATP) production are already apparent at 17 days of age.
de Groof
A J
AJ
Department of Cell Biology, Nijmegen Center for Molecular Life Sciences, University Medical Center, University of Nijmegen, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands.
Oerlemans
F T
FT
Jost
C R
CR
Wieringa
B
B
D000818:Animals; D003402:Creatine Kinase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006019:Glycolysis / Q000235:genetics*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D018272:Porins / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels
D018272:Porins; D050994:Voltage-Dependent Anion Channels; D000226:Mitochondrial ADP, ATP Translocases; D007770:L-Lactate Dehydrogenase; D003576:Electron Transport Complex IV; D003402:Creatine Kinase