Altered mitochondrial sensitivity for ADP and maintenance of creatine-stimulated respiration in oxidative striated muscles from VDAC1-deficient mice.
Voltage-dependent anion channels (VDACs) form the main pathway for metabolites across the mitochondrial outer membrane. The mouse vdac1 gene has been disrupted by gene targeting, and the resulting mutant mice have been examined for defects in muscle physiology. To test the hypothesis that VDAC1 constitutes a pathway for ADP translocation into mitochondria, the apparent mitochondrial sensitivity for ADP (Km(ADP)) and the calculated rate of respiration in the presence of the maximal ADP concentration (Vmax) have been assessed using skinned fibers prepared from two oxidative muscles (ventricle and soleus) and a glycolytic muscle (gastrocnemius) in control and vdac1(-/-) mice. We observed a significant increase in the apparent Km((ADP)) in heart and gastrocnemius, whereas the V(max) remained unchanged in both muscles. In contrast, a significant decrease in both the apparent Km((ADP)) and V(max) was observed in soleus. To test whether VDAC1 is required for creatine stimulation of mitochondrial respiration in oxidative muscles, the apparent Km((ADP)) and Vmax were determined in the presence of 25 mm creatine. The creatine effect on mitochondrial respiration was unchanged in both heart and soleus. These data, together with the significant increase in citrate synthase activity in heart, but not in soleus and gastrocnemius, suggest that distinct metabolic responses to altered mitochondrial outer membrane permeability occur in these different striated muscle types.
Anflous
K
K
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Armstrong
D D
DD
Craigen
W J
WJ
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002950:Citrate (si)-Synthase / Q000378:metabolism; D006352:Heart Ventricles / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D018272:Porins / Q000235:genetics / Q000502:physiology*; D050995:Voltage-Dependent Anion Channel 1; D050994:Voltage-Dependent Anion Channels
D018272:Porins; C494763:Vdac1 protein, mouse; D050994:Voltage-Dependent Anion Channels; D000244:Adenosine Diphosphate; D050995:Voltage-Dependent Anion Channel 1; D002950:Citrate (si)-Synthase