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. Author manuscript; available in PMC: 2012 Dec 4.
Published in final edited form as: Cell Rep. 2012 Nov 1;2(5):1137–1142. doi: 10.1016/j.celrep.2012.10.001

Figure 4. XJB-5-131 improves mitochondrial function in HD150KI animals.

Figure 4

(A) Simplified diagram of electron transport chain and its inhibitors. Rotenone, antimycin A, and oligomycin are the inhibitors of Complex I, Complex III, and ATP synthase, respectively. Fluoro-carbonyl cyanide phenylhydrazone (FCCP) is an ionophore, which allows re-entry of the protons into the mitochondrial matrix and dissipates the proton gradient. (B) Representative profiles showing effects of XJB-5-131 treatment on oxygen consumption rates (OCR) under basal conditions and upon injections of mitochondrial inhibitors in isolated striatal synaptosomes from 57-week HD150KI mice. Each profile represents one independent biological experiment analyzed in triplicate. Data are means ± SEM (n = 3). The arrows indicate the injection of mitochondrial inhibitors. Three independent experiments were performed to obtain quantification of mitochondrial spare respiratory capacity (SRC) presented in (C). (C) Effects of XJB-5-131 treatment on SRC in isolated striatal synaptosomes. SRC is defined as the OCR difference between FCCP-induced respiration and basal respiration. Data represent three independent experiments and each was performed with five HD150KI mice and analyzed in triplicate. Data are mean ± SEM (n = 3). *P < 0.05, **, P < 0.01 using the unpaired two-tailed Student's t-test. (D) Schematic diagram illustrating the working hypothesis of DMNQ and XJB-5-131 within MT. (E) Representative profiles showing effects of DMNQ on OCR in the absence and presence of XJB-5-131 under basal conditions and upon injection of mitochondrial inhibitors. The down arrows indicate the injection of mitochondrial inhibitors. Each profile represents one independent biological experiment analyzed in triplicate. Data are means ± SEM (n = 3). Three independent experiments were performed to obtain quantification of mitochondrial SRC presented in (F). (F) XJB-5-131 treatment significantly improves mitochondrial SRC in 57-week HD150KI mouse striatal synaptosomes resulting from 1 µM DMNQ exposure. Data are normalized to the control (in the absence of both XJB-5-131 and DMNQ) and are representative of three independent experiments. In each experiment, three HD150KI mice were used and analyzed in triplicate. Data are mean ± SEM (n = 3). *, P < 0.05 using the unpaired two-tailed Student's t-test. XJB-5-131 is abbreviated as XJB in the figures. See also Figure S2.