title: The universality of bioenergetic disease and amelioration with redox therapy.
abstract: Overt mitochondrial diseases associated with mitochondrial DNA mutations are characterized by a decline in mitochondrial respiratory function. Similarly, a progressive decline in mitochondrial respiratory function associated with mitochondrial DNA mutations is clearly evidenced in aged human subjects. This communication is concerned with the development of a rat model for the study of bioenergy decline associated with the ageing process and overt mitochondrial diseases. The model involves the treatment of young rats with AZT to induce skeletal and cardiac myopathies. It has shown that there is a decline in soleus muscle function in vivo and that this decline is mirrored in the capacity of heart sub-mitochondrial particles to maintain bioenergy function. Coenzyme Q10 and several analogs were administered with AZT as potential therapeutics for the re-energization of affected tissues. Coenzyme Q10 and especially decyl Q were found to be therapeutically beneficial by both in vivo improvement in soleus muscle function and in vitro cardiac mitochondrial membrane potential capacity. Sub-mitochondrial particles were also prepared from heart mitochondria of young and aged rats. The particles prepared from the aged rats were found to have a decreased ability to maintain membrane potential as compared to those derived from the young rats.
authors.affiliation: Centre for Molecular Biology and Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: A W
authors.initials: AW
authors.lastname: Linnane
authors.forename: M
authors.initials: M
authors.lastname: Degli Esposti
authors.forename: M
authors.initials: M
authors.lastname: Generowicz
authors.forename: A R
authors.initials: AR
authors.lastname: Luff
authors.forename: P
authors.initials: P
authors.lastname: Nagley
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy*; D003067:Coenzymes; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D017240:Mitochondrial Myopathies / Q000139:chemically induced / Q000188:drug therapy*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010084:Oxidation-Reduction; D051381:Rats; D013367:Submitochondrial Particles / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015215:Zidovudine / Q000633:toxicity*
chemical_list: D003067:Coenzymes; D014451:Ubiquinone; D015215:Zidovudine; C024989:coenzyme Q10