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Clorgyline and other propargylamine derivatives as inhibitors of succinate-dependent H2O2 release at NADH:UBIQUINONE oxidoreductase (Complex I) in brain mitochondria

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Abstract

Complex I is the main O2 − producer of the mitochondrial respiratory chain. O2 − release is low with NAD-linked substrates and increases strongly during succinate oxidation, which increases the QH2/Q ratio and is rotenone sensitive. We show that the succinate dependent O2 − production (measured as H2O2 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 ΔpH modifications. Mitochondrial respiration is similarly unaffected. The propargylamines inhibition of O2 −/H2O2 production is monitored also in the presence of the Parkinson's disease toxin dopaminochrome which stimulates O2 − release. Propargylamine-containing compounds are the first pharmacological inhibitors described for O2 − release at Complex I.

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Authors and Affiliations

  1. Dipartimento di Chimica Biologica and Istituto di Neuroscienze, Sezione di Biomembrane (Consiglio Nazionale delle Ricerche), Università di Padova, Viale G.Colombo 3, 35121, Padova, Italy

    Franco Zoccarato, Mara Cappellotto & Adolfo Alexandre

  2. Dipartimento di Chimica Biologica, Università di Padova, Viale G.Colombo 3, 35121, Padova, Italy

    Adolfo Alexandre

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  1. Franco Zoccarato
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  2. Mara Cappellotto
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  3. Adolfo Alexandre
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Correspondence to Adolfo Alexandre.

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Zoccarato, F., Cappellotto, M. & Alexandre, A. Clorgyline and other propargylamine derivatives as inhibitors of succinate-dependent H2O2 release at NADH:UBIQUINONE oxidoreductase (Complex I) in brain mitochondria. J Bioenerg Biomembr 40, 289–296 (2008). https://doi.org/10.1007/s10863-008-9160-z

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  • DOI: https://doi.org/10.1007/s10863-008-9160-z

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