IMPAIRMENT OF RESPIRATORY FUNCTIONS IN MITOCHONDRIA OF RATS WITH AN INHERITED HYPERPRODUCTION OF FREE-RADICALS

The functional characteristics of liver mitochondria and physical-chem ical properties of mitochondrial membranes were studied in S rats with congenitally enhanced capacity to free radical generation in comparis on to those in Wistar rats. It was shown previously that intense lipid peroxidation, numerous DNA rearrangements, protein oxydation, morbid states resembling human degenerative diseases and short life-span are characteristic of S rats. In present study we have demonstrated that i n S rats at the age of 2-3 months the respiratory rate of the mitochon dria in active metabolic state is lower than in Wistar rats, and so ar e the values for the respiratory control ratio, oxidative phosphorylat ion and membrane potential. By 10-12 months of age the decrease of the respiration rate and oxidative phosphorylation in S rat mitochondria become even more dramatic. These changes are associated with a decreas e in the extent of dip of proteins into the membrane lipid layer or wi th the increase in the amount of protein aggregates. The results add t o the understanding of the nature of morbid conditions developed under the effect of intensive free radical generation and to the comprehens ion of their role in aging. (C) 1994 Academic Press, Inc.