CORRELATION BETWEEN MITOCHONDRIAL-DNA 4977-BP DELETION AND RESPIRATORY-CHAIN ENZYME-ACTIVITIES IN AGING HUMAN SKELETAL-MUSCLES

The content of the mitochondrial DNA 4977-bp deletion and the respirat ory chain enzyme activities were determined in the same human skeletal muscle specimens. A direct correlation between damage to mtDNA and bi oenergetic deficiency was observed. The time-course of the appearance of the mtDNA deletion was followed. The highest percentage of mtDNA-de leted molecules was 0.26% and it was found in the eighties which corre sponds to the age of the major reduction in the respiratory chain enzy me activities. Two samples with very low mitochondrial respiratory enz yme activities exhibited much higher levels of deletion compared to th e similar age counterparts. Given, however, the low absolute level of the deletion also in these samples, we suggest that damage to the resp iratory chain complexes, especially complex IV, might be the cause mor e than the effect of the increased number of mtDNA molecules bearing d eletions in aged human skeletal muscle. (C) 1994 Academic Press, Inc.