Impaired Energy Production Contributes to Development of Failure in Taurine Deficient Heart

Abstract

Taurine forms a conjugate in the mitochondria with a uridine residue in the wobble position of tRNA^Leu(UUR). The resulting product, 5-taurinomethyluridine tRNA^Leu(UUR), increases the interaction between the UUG codon and AAU anticodon of tRNA^Leu(UUR), thereby improving the decoding of the UUG codon. We have shown that the protein most affected by the taurine conjugation product is ND6, which is a subunit of complex I of the respiratory chain. Thus, taurine deficiency exhibits reduced respiratory chain function. Based on these findings, we proposed that the taurine deficient heart is energy deficient. To test this idea, hearts were perfused with buffer containing acetate and glucose as substrates. The utilization of both substrates, as well as the utilization of endogenous lipids, was significantly reduced in the taurine deficient heart. This led to a 25% decrease in ATP production, an effect primarily caused by diminished aerobic metabolism and respiratory function. In addition, inefficient oxidative phosphorylation causes a further decrease in ATP generation. The data support the idea that reductions in energy metabolism, including oxidative phosphorylation, ATP generation and high energy phosphate content, contribute to the severity of the cardiomyopathy. The findings are also consistent with the hypothesis that taurine deficiency and reduced myocardial energy content increases mortality of the taurine deficient, failing heart. The clinical implications of these findings are addressed.

Keywords: Cardiac work-oxidative phosphorylation relationship; Glucose oxidation; Metabolic shift in heart failure; Mitochondrial ATP production; Taurine-mediated regulation of complex I activity.