An updating of the biochemical function of coenzyme Q in mitochondria.
The apparent Km for coenzyme Q10 in NADH oxidation by coenzyme Q (CoQ)-extracted beef heart mitochondria is close to their CoQ content, whereas both succinate and glycerol-3-phosphate oxidation (the latter measured in hamster brown adipose tissue mitochondria) are almost saturated at physiological CoQ concentration. Attempts to enhance NADH oxidation rate by excess CoQ incorporation in vitro were only partially successful: the reason is in the limited amount of CoQ10 that can be incorporated in monomeric form, as shown by lack of fluorescence quenching of membrane fluorescent probes; at difference with CoQ10, CoQ5 quenches probe fluorescence and likewise enhances NADH oxidation rate above normal. Attempts to enhance the CoQ content in perfused rat liver and in isolated hepatocytes failed to show uptake in the purified mitochondrial fraction. Nevertheless CoQ cellular uptake is able to protect mitochondrial activities. Incubation of hepatocytes with adriamycin induces loss of respiration and mitochondrial potential measured in whole cells by flow cytometry using rhodamine 123 as a probe: concomitant incubation with CoQ10 completely protects both respiration and potential. An experimental study of aging in the rat has shown some decrease of mitochondrial CoQ content in heart, and less in liver and skeletal muscle. In spite of the little change observed, it is reasoned that CoQ administration may be beneficial in the elderly, owing to the increased demand for antioxidants.
Lenaz
G
G
Dipartimento di Biochimica Giovanni Moruzzi, Universita' di Bologna, Italy.
Fato
R
R
Castelluccio
C
C
Cavazzoni
M
M
Estornell
E
E
Huertas
J F
JF
Pallotti
F
F
Parenti Castelli
G
G
Rauchova
H
H
D000375:Aging / Q000378:metabolism; D000818:Animals; D002417:Cattle; D006224:Cricetinae; D004041:Dietary Fats / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004579:Electron Transport / Q000502:physiology; D004734:Energy Metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D014451:Ubiquinone / Q000493:pharmacokinetics / Q000502:physiology*
D004041:Dietary Fats; D009097:Multienzyme Complexes; D009243:NAD; D014451:Ubiquinone; D004317:Doxorubicin; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases