VARIATIONS OF MUSCLE MITOCHONDRIAL CREATINE-KINASE ACTIVITY IN MITOCHONDRIAL DISEASES

Mitochondrial creatine kinase (mtCK) activity has been measured in the mitochondria isolated from the muscle of 69 patients suspected of mit ochondrial diseases. The isolated mitochondria did not contain signifi cant amounts of the muscle isoform of creatine kinase, as checked by a n immunoassay performed after electrophoretic separation of the variou s isoforms. Hence, the enzyme assay reliably represented the mtCK acti vity. Therefore, a simple measurement of CK activity in isolated mitoc hondria permitted the measurement of mtCK activity. An absence of mtCK activity in muscle was never observed. The lowest activities were not associated to defined mitochondrial diseases Linked to defects of res piratory chain complexes or to defects of citric cycle enzymes. On the contrary, mtCK activity was significantly increased in the muscle of patients exhibiting ragged red fibers. This increase was generally ass ociated to an increase of citrate synthase activity. Since ragged-red fibers and elevated mtCK activities were generally not found in childr en younger than 3 years, even in cases of characteristic oxidative pho sphorylation deficiency, it is suggested that the increase in mtCK act ivity as well as the appearance of ragged-red fibers are not the first events which occur during the evolution of mitochondrial diseases but would rather be long-term secondary processes which slowly develop in deficient mitochondria.