Quantitative proteomic study of myocardial mitochondria in urea transporter B knockout mice

In previous research, we showed that 16‐week‐old urea transporter B (UT‐B) null mice have an atrial–ventricular conduction block, and hypothesized myocardial mitochondrial dysfunction. To investigate the mechanism of this block, we examined the proteomic differences in the myocardial mitochondria of UT‐B null and wild‐type mice with nanoscale LC–MS/MS. Of 26 proteins clearly downregulated in the UT‐B null mice, 15 are involved in complexes I, III, IV, and V of the respiratory chain, which would strongly reduce the activity of the electron transport chain. Excess electrons from complexes I and III pass directly to O2 to generate ROS and deplete ROS‐scavenging enzymes. Myocardial intracellular ROS were significantly higher in UT‐B null mice than in wild‐type mice (p < 0.01), constituting an important cause of oxidative stress injury in the myocardia of UT‐B null mice. The mitochondrial membrane potential (ΔΨm) was also lower in UT‐B null mice than in wild‐type mice (p < 0.05), causing oxidative phosphorylation dysfunction of complex V and insufficient ATP in the myocardial cells of UT‐B null mice. HADHA (a trifunctional protein) and HSP60 were also downregulated in the UT‐B null myocardial mitochondria. These results confirm that mitochondrial dysfunction underlies the pathogenesis of the atrial–ventricular conduction block in UT‐B null mice.