Maintained coupling of oxidative phosphorylation to creatine kinase activity in sarcomeric mitochondrial creatine kinase-deficient mice.
The importance of mitochondrial creatine kinase (mi-CK) in oxidative muscle was tested by studying the functional properties of in situ mitochondria in saponin-skinned muscle fibres from sarcomeric mi-CK-deficient (mutant) mice. Biochemical analyses showed that the lack of mi-CK in mutant muscle was associated with a decrease in specific activity of MM-CK in mutant ventricle, and increase in mutant soleus (oxidative) muscle. Lactate dehydrogenase activity and isoenzyme analysis showed an increased glycolytic metabolism in mutant soleus. No change was observed in ventricular muscle. In control animals, the apparent K(m) of mitochondrial respiration for ADP in ventricle and soleus (232 +/- 36 and 381 +/- 63 microM, respectively) was significantly reduced in the presence of creatine (52 +/- 8 and 45 +/- 12 microM, respectively). There was no change in the K(m) in oxidative fibres from mutant mice (258 +/- 27 and 399 +/- 66 microM, respectively) compared with control, though surprisingly, it was also significantly decreased in the presence of creatine (144 +/- 8 and 150 +/- 27 microM, respectively) despite the absence of mi-CK. It is proposed that in mutant (and perhaps normal) oxidative tissue, cytosolic MM-CK can relocate to the outer mitochondrial membrane, where it is coupled to oxidative phosphorylation by close proximity to porin, and the adenine nucleotide translocase. Such an effect can preserve the functioning of the CK shuttle and the energetic properties of mi-CK deficient tissue.
Boehm
E
E
Laboratoire de Cardiologie Cellulaire et Moleculaire, INSERM U-446, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
Veksler
V
V
Mateo
P
P
Lenoble
C
C
Wieringa
B
B
Ventura-Clapier
R
R
D000818:Animals; D003402:Creatine Kinase / Q000172:deficiency / Q000378:metabolism*; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008931:Mitochondria, Muscle / Q000201:enzymology*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D012518:Sarcomeres / Q000201:enzymology*
D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase