Thyroid Hormone Regulation of the NADH Shuttles in Liver and Cardiac Mitochondria

T. D. Scholz, C. J. TenEyck and B. C. Schutte. Thyroid Hormone Regulation of the NADH Shuttles in Liver and Cardiac Mitochondria. Journal of Molecular and Cellular Cardiology (2000) 32, 1–10. Thyroid hormone can potentially regulate the malate/aspartate and α -glycerophosphate shuttle pathways in cardiac mitochondria either directly, by altering gene expression, or indirectly, by increasing myocardial workload. The goal of the current study was to determine the influence of thyroid hormone on the NADH shuttles in cardiac and liver mitochondria. Malate/aspartate andα -glycerophosphate shuttle capacities were significantly increased in cardiac mitochondria from adult rats treated for 9 days with T3 compared to saline-treated controls. Liver mitochondria demonstrated a significant increase in α -glycerophosphate and no change in malate/aspartate shuttle capacity. T3 increased steady-state mRNA levels and activity of mitochondrial α -glycerophosphate dehydrogenase in both myocardium and liver. Quantitative immunoblot studies demonstrated a significant increase in aspartate-glutamate carrier levels in T3-treated myocardium suggesting a regulatory role of the aspartate/glutamate carrier in T3-treated hearts. Thyroid hormone effects on the NADH shuttles are tissue-specific. Changes in the NADH shuttles in the presence of thyroid hormone excess occur both directly at the gene level and indirectly as an adaptive response.