Figure 4.

High-frequency [¹H]-¹³C NMR spectroscopy suggests that parkin-facilitated clearance of defective mitochondria attenuates oxidative stress and restores TCA cycle activity. High-frequency [¹H]-¹³C NMR spectroscopy showing (A) histograms that represent metabolic flux of ¹³C label from glucose into Succ C2/C3 and Lac C3; (B) metabolic pool size of Succ and Lac; (C) metabolic flux into Glu C4, (D) Gln C4 and (E) GABA C2; (F) metabolic pool size of Glu, Gln and GABA. (G) Schematic representation of neuronal and astrocytic compartments, depicting Glu–Gln cycle, cytosolic and mitochondrial metabolism and the effects of Aβ on cell compartmentalization. Aβ decreases ¹³C flux into the mitochondria and stimulates Lac production resulting in oxidative stress. Aβ decreases TCA-derived neurotransmitters Glu and GABA and depresses the Glu–Gln cycle. Parkin decreases the levels of intracellular Aβ, enhances ¹³C flux into mitochondrial TCA cycle and decreases Lac production, thus alleviating oxidative stress. Parkin reverses Aβ-induced decrease in Glu and GABA levels via amelioration of TCA cycle activity, which is independent of Glu–Gln cycle, restoring synaptic neurotransmitter balance. TCA, tricarboxylic acid; Glu, glutamate; Gln, glutamine; GABA, γ-amino butyric acid; Succ, succinate; Lac, lactate. Asterisk is significantly different to contralateral or as indicated, P< 0.05, t-test. Data are mean ± SD; n= 4.