Effect of aging on the oxidative phosphorylation pathway.
The proposed study was undertaken to investigate the effect of aging on control of the oxidative phosphorylation pathway. Flux control coefficients for adenine nucleotide translocase and cytochrome c oxidase were determined using the procedure of Groen et al. [J. Biol. Chem., 257 (1982) 137-144]. Hepatic mitochondrial fractions from Fischer 344 rats were isolated from control (average age 6.5 months), and aged (average age 27.3 months) groups. No aging-related changes in the extent of control of respiration by the oxidase were obtained, however, differences were observed for the translocase. For the control group of animals, the greatest regulation occurred at 80-85% maximal respiratory rates, and declined at higher rates. For the aged group, a similar flux control coefficient was obtained at 80-85% respiration, but was maintained as respiration increased to maximal rates. It is proposed that changes in the flux control coefficients at maximal respiratory rates are associated with an aging-related decrease in translocase activity. Evaluation of translocase content revealed no significant differences between the two groups supporting the concept that the decreased activity was not due to decreased content. During the course of these experiments, it also became apparent that there was a significant aging-related decrease in the rate of succinate oxidation providing an adequate supply of ADP was present. No significant changes in respiratory rates, or RCR, were evident at suboptimal concentrations of ADP as reported previously from this laboratory [Vorbeck, M.L. et al., Arch. Biochem. Biophys., 214 (1982) 67-79]. Since similar decreases in respiration were obtained upon addition of an uncoupler, the aging-related changes in respiration are attributed to differences at the level of the electron transport system, including its associated reactions. The aging-related differences in respiratory rates, and extent of control of respiration, were both observed under conditions of maximal stimulation of respiration. This suggests an inability of mitochondria from aged animals to respond to the increased demands of oxidation. Basic to these differences may be the lipid-membrane associated changes seen during aging.
Darnold
J R
JR
Department of Pathology, University of Missouri School of Medicine, Columbia 65212.
Vorbeck
M L
ML
Martin
A P
AP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000244:Adenosine Diphosphate; D000226:Mitochondrial ADP, ATP Translocases; D003576:Electron Transport Complex IV