Coenzyme Q deficiency in mitochondria: kinetic saturation versus physical saturation.
The coenzyme Q (CoQ) concentration in the inner membrane of beef heart mitochondria is not kinetically saturating for NADH oxidation inasmuch as the K(m) of NADH oxidation for endogenous CoQ10 is in the mM range in membrane lipids. Using CoQ1 as an electron acceptor from complex I, we have found additional evidence that the high Km of NADH oxidase for CoQ is not an artifact due to the use of organic solvents in reconstitution studies. We have also obtained experimental evidence that CoQ concentration may be rendered more rate-limiting for NADH oxidation either by a decrease of CoQ content (as in liver regeneration or under an acute oxidative stress), or by a possible increase of the Km for CoQ, as in some mitochondrial diseases and ageing. The possibility of enhancing the rate of NADH oxidation by CoQ therapy is hindered by the fact that the CoQ concentration in mitochondria appears to be regulated by its mixability with the membrane phospholipids. Nevertheless CoQ10 incorporated into heart submitochondrial particles by sonication enhances NADH oxidation (but not succinate oxidation) up to twofold. Nontoxic CoQ homologs and analogs having shorter side-chains with respect to CoQ10 can be incorporated in the mitochondrial membrane without sonication, supporting an enhancement of NADH oxidation rate above 'physiological' values. It is worth investigating whether this approach can have a therapeutical value in vivo in mitochondrial bioenergetic disorders.
Lenaz
G
G
Department of Biochemistry G. Moruzzi, Bologna, Italy.
Parenti Castelli
G
G
Fato
D'Aurelio
M
M
Bovina
C
C
Formiggini
G
G
Marchetti
M
M
Estornell
E
E
Rauchova
H
H
D000375:Aging / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003067:Coenzymes; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D006333:Heart Failure / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008051:Lipid Bilayers; D008115:Liver Regeneration; D008563:Membrane Lipids / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism*
D003067:Coenzymes; D008051:Lipid Bilayers; D008563:Membrane Lipids; D009097:Multienzyme Complexes; D014451:Ubiquinone; C060262:2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; C024989:coenzyme Q10