Clorgyline and other propargylamine derivatives as inhibitors of succinate-dependent H sub(2)O sub(2) release at NADH:Ubiquinone oxidoreductase (Complex I) in brain mitochondria

• Published in: Journal of bioenergetics and biomembranes Vol. 40; no. 4; pp. 289 - 296
• Main Authors: Zoccarato, Franco, Cappellotto, Mara, Alexandre, Adolfo
• Format: Journal Article
• Language: English
• Published: 01.08.2008
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-008-9160-z

Complex I is the main O sub(2) super(-) producer of the mitochondrial respiratory chain. O sub(2) super(-) release is low with NAD-linked substrates and increases strongly during succinate oxidation, which increases the QH sub(2)/Q ratio and is rotenone sensitive. We show that the succinate dependent O sub(2) super(-) production (measured as H sub(2)O sub(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 pH modifications. Mitochondrial respiration is similarly unaffected. The propargylamines inhibition of O sub(2) super(-)/H sub(2)O sub(2) production is monitored also in the presence of the Parkinson's disease toxin dopaminochrome which stimulates O sub(2) super(-) release. Propargylamine-containing compounds are the first pharmacological inhibitors described for O sub(2) super(-) release at Complex I.