THE UNIVERSALITY OF BIOENERGETIC DISEASE AND AMELIORATION WITH REDOX THERAPY

Overt mitochondrial diseases associated with mitochondrial DNA mutatio ns are characterized by a decline in mitochondrial respiratory functio n. Similarly, a progressive decline in mitochondrial respiratory funct ion associated with mitochondrial DNA mutations is clearly evidenced i n aged human subjects. This communication is concerned with the develo pment of a rat model for the study of bioenergy decline associated wit h the ageing process and overt mitochondrial diseases. The model invol ves the treatment of young rats with AZT to induce skeletal and cardia c myopathies. It has shown that there is a decline in soleus muscle fu nction in vivo and that this decline is mirrored in the capacity of he art sub-mitochondrial particles to maintain bioenergy function. Coenzy me Q(10) and several analogs were administered with AZT as potential t herapeutics for the re-energization of affected tissues. Coenzyme Q(10 ) and especially decyl Q were found to be therapeutically beneficial b y both in vivo improvement in soleus muscle function and in vitro card iac mitochondrial membrane potential capacity. Sub-mitochondrial parti cles were also prepared from heart mitochondria of young and aged rats . The particles prepared from the aged rats were found to have a decre ased ability to maintain membrane potential as compared to those deriv ed from the young rats.