A redox reaction between MPP + and MPDP + to produce superoxide radicals does not impair mitochondrial function

Abstract

Rat brain mitochondria were incubated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and its two metabolites (1-methyl-4-phenyl-2,3-dihydropyridium (MPDP +) and 1-methyl-4-phenylpyridinium (MPP +), and O 2 uptake was assessed. MPP + (500 and 1000 μM) inhibited state 3 and state 4 respiration with a reduction in the respiratory control ratio (RCR). In the presence of MPTP or MPDP + (100–1000 μM) no inhibition of mitochondrial function occurred. Incubation with MPP + (100–1000 μM) in combination with equimolar concentrations of MPDP + or MPTP (100–1000 μM) did not increase the inhibition of mitochondrial function produced by MPP + alone. Inhibition of mitochondrial function produced by MPP + (500 μM) was not reduced by incorporation of superoxide dismutase (SOD) (50–1000 units/mL). However, the RCR in the presence of 500 μM MPP + and 1000 units/mL SOD was not different from control values. SOD did not prevent the inhibition of state 3 and state 4 respiration produced by the combination of MPP + and MPDP +. The results suggest that a redox reaction between MPP + and MPDP + to generate superoxide radicals does not contribute to the impairment of mitochondrial function produced by MPTP administration.