Succinate modulation of H2O2 release at NADH:ubiquinone oxidoreductase (Complex I) in brain mitochondria.
Complex I (NADH:ubiquinone oxidoreductase) is responsible for most of the mitochondrial H2O2 release, both during the oxidation of NAD-linked substrates and during succinate oxidation. The much faster succinate-dependent H2O2 production is ascribed to Complex I, being rotenone-sensitive. In the present paper, we report high-affinity succinate-supported H2O2 generation in the absence as well as in the presence of GM (glutamate/malate) (1 or 2 mM of each). In brain mitochondria, their only effect was to increase from 0.35 to 0.5 or to 0.65 mM the succinate concentration evoking the semi-maximal H2O2 release. GM are still oxidized in the presence of succinate, as indicated by the oxygen-consumption rates, which are intermediate between those of GM and of succinate alone when all substrates are present together. This effect is removed by rotenone, showing that it is not due to inhibition of succinate influx. Moreover, alpha-oxoglutarate production from GM, a measure of the activity of Complex I, is decreased, but not stopped, by succinate. It is concluded that succinate-induced H2O2 production occurs under conditions of regular downward electron flow in Complex I. Succinate concentration appears to modulate the rate of H2O2 release, probably by controlling the hydroquinone/quinone ratio.
Zoccarato
Franco
F
Dipartimento di Chimica Biologica and the Istituto di Neuroscienze, Sezione di Biomembrane, Consiglio Nazionale delle Ricerche, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Cavallini
Lucia
L
Bortolami
Silvia
S
Alexandre
Adolfo
A
D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007656:Ketoglutaric Acids / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013379:Substrate Specificity / Q000187:drug effects; D013386:Succinates / Q000494:pharmacology*; D017186:Titrimetry
D007656:Ketoglutaric Acids; D008293:Malates; D013386:Succinates; D018698:Glutamic Acid; C030298:malic acid; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I