High resolution respirometry reveals a respiration defect in <i>PARK2^−/−</i> mice.

<p>(<b>A</b>) Representative experiment with striatal post-nuclear supernatant. Blue curve = oxygen concentration (O₂) expressed as nmol/mL; red curve = rate of oxygen consumption expressed as nmoles O₂/mL and min; successive additions: ADP = 1 mM ADP in the medium with 10 mM glutamate+5 mM malate; OM = 1 µg/mL oligomycin, cccp = successive additions of 1.25 µM (up to the maximal respiration rate independent from ATP synthase capacity); KCN = 1 mM KCN (non-respiratory oxygen consumption); (<b>B, C, D</b>) Bars showing state 3 respiration, state 4 respiration and respiratory reserve on complex I substrates (glutamate+malate) in post-nuclear supernatants from (B) striatum, (C) midbrain and (D) liver of 24- and 9-month-old <i>PARK2^−/−</i> (black bars) and wild type mice (white bars); all data are expressed as nmoles O₂/mL and mg proteins and shown as means ± SD; two animals, one per genotype, were analyzed the same day; the data were obtained from 6 to 8 individual animals of each genotype. * <i>p</i><0.05 using Mann and Whitney test. In liver, state 3 respiration rate and respiratory reserve significantly decreased with age in both wild type mice (p = 0.011 and <0.001 when comparing state 3 respiration and respiratory reserve respectively between 9 and 24 months of age using Mann and Whitney test) and in <i>PARK2^−/−</i> mice (p = 0.019 and <0.001 when comparing state 3 respiration and respiratory reserve respectively between 9 and 24 months of age using Mann and Whitney test).