D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease
J. Clin. Invest. Kim Tieu, et al. 112:892 doi:10.1172/JCI18797 [
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Figure 4DβHB increases oxygen consumption in purified brain mitochondria. Mitochondria (300 μg) were incubated in the absence or presence of MPP
+ (5 minutes;
a) or rotenone (2.5 minutes;
b) at 30°C, and then 5 mM DβHB was added to induce oxygen consumption. DβHB attenuated inhibition of mitochondrial respiration induced by MPP
+ (
a) or rotenone (
b) at indicated concentrations, which blocked about 25–90% of oxygen consumption when glutamate and malate were used as NADH-linked substrates (data not shown). (
c) The improvement of oxygen consumption by DβHB is stereospecific and is blocked by 10 mM 3-NP, a complex II inhibitor. (
d) DβHB increases oxygen consumption in a dose-dependent and saturable fashion as seen with succinate, a complex II substrate, although not as efficiently as succinate does on an equimolar basis.
n = 3–4.