Effect of the overexpression of Mfn2 or the truncated Mfn2 mutant on mitochondrial function in GCDCA-treated L02 cells.

<p>The overexpression of Mfn2 or truncated Mfn2 (A) protected cell viability in L02 cells, (B) reversed the reduction in ATP levels, (C) ameliorated the decrease in ΔΨm, and (D) reduced the excess ROS production following treatment with GCDCA. The results are expressed as a percentage of the control value, which was set at 100%. The values are the means ± SEM. *P<0.05 versus the control group, <b>^#</b>P<0.05, <b>^##</b>P<0.01 versus the GCDCA group, n = 6.</p

Effect of the overexpression of Mfn2 or the truncated Mfn2 mutant on mitochondrial morphology and mitochondrial function in GCDCA-treated L02 cells.

<p>(A) Western blot analysis was used to detect the expression of Mfn2-GFP and the truncated Mfn2 mutant transfected into L02 cells. (B) Confocal microscope photographs indicated increased mitochondrial localization of Mfn2 and the truncated Mfn2 mutant and their roles in mitochondrial morphology. (C) Proportions of cells with fragmented mitochondrial pattern was determined in at least six different cultures under basal conditions (untreated), and after the L02 cells were treated with various doses (25, 50, 75, or 100 µM) of GCDCA for 6 h. The results are expressed as a percentage of the control value, which was set at 100%. The values are the means ± SEM. *P<0.05 versus the control group, <b>^#</b>P<0.05, <b>^##</b>P<0.01 versus the GCDCA group, n = 6.</p

Mitochondrial dysfunction and loss of the mitochondrial fusion protein Mfn2 in patients with extrahepatic cholestasis.

<p>(A) Representative histology of human liver tissue. (B) The MDA concentrations and (C) ATP concentrations in human liver tissue were determined using a MDA Determination Kit and an ATP Determination Kit. (D) Representative immunoblot and quantification analysis of the protein level of Mfn2 (86 kDa) in human liver tissue. β-actin (42 kDa) was the internal standard for protein loading. The results are expressed as a percentage of the control value, which was set at 100%. The values are the means ± SEM. *P<0.05 versus the control group.</p

Clinical characteristics of the patients.

<p>Clinical characteristics of the patients.</p

GCDCA-induced impairment of mitochondrial function in the treated L02 cells (A) Cell viability, (B) ATP concentrations, (C) ΔΨm, and (D) ROS production were assayed.

<p>The L02 cells were treated with various doses (25, 50, 75, or 100 µM) of GCDCA for 6 h. The results were expressed as a percentage of the control value, which was set at 100%. The values are the means ± SEM. *P<0.05 versus the control group, n = 6.</p