title: Clorgyline and other propargylamine derivatives as inhibitors of succinate-dependent H(2)O(2) release at NADH:UBIQUINONE oxidoreductase (Complex I) in brain mitochondria.
abstract: Complex I is the main O(2)(-) producer of the mitochondrial respiratory chain. O(2)(-) release is low with NAD-linked substrates and increases strongly during succinate oxidation, which increases the QH(2)/Q ratio and is rotenone sensitive. We show that the succinate dependent O(2)(-) production (measured as H(2)O(2) release) is inhibited by propargylamine containing compounds (clorgyline, CGP 3466B, rasagiline and TVP-1012). The inhibition does not affect membrane potential and is unaffected by DeltapH modifications. Mitochondrial respiration is similarly unaffected. The propargylamines inhibition of O(2)(-)/H(2)O(2) production is monitored also in the presence of the Parkinson's disease toxin dopaminochrome which stimulates O(2)(-) release. Propargylamine-containing compounds are the first pharmacological inhibitors described for O(2)(-) release at Complex I.
authors.affiliation: Dipartimento di Chimica Biologica and Istituto di Neuroscienze, Sezione di Biomembrane (Consiglio Nazionale delle Ricerche), Università di Padova, Padova, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Zoccarato
authors.forename: Mara
authors.initials: M
authors.lastname: Cappellotto
authors.forename: Adolfo
authors.initials: A
authors.lastname: Alexandre