Fig. 2. Synergistic effect of Bcs1l^p.S78G and mt-Cyb^p.D254N on CIII activity.

a–h CIII activity in liver (a, b) and kidney mitochondrial fractions (c, d) and heart (e, f) and skeletal muscle homogenates (g) from F1 hybrid progeny (a, c, e, g) and from mice backcrossed to C57BL/6JCrl (b, d, f, h). CIII activity data from isolated liver and kidney mitochondria were normalized to mitochondrial protein amount. The data from muscle and heart homogenates were normalized to relative respiratory chain content as assessed by measuring cyanide-sensitive cytochrome c oxidation. Cardiac and skeletal muscle homogenate CIII activity relative to tissue protein are shown in Supplementary Fig. 5. The orange line represents 50% residual activity, a threshold for appearance of hypoglycemic and hepatic manifestations in Bcs1l mutant mice. The red line represents 25% residual activity, a value observed in the liver of Bcs1l mutant mice in the colony with short survival at the onset of the terminal stage. Statistics: one-way ANOVA followed by planned comparisons. Error bars represent 95% CI of the mean.