Thyroid hormone regulation of the NADH shuttles in liver and cardiac mitochondria

Thyroid hormone can potentially regulate the malate/aspartate and alpha-gly cerophosphate 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 ho rmone on the NADH shuttles in cardiac and liver mitochondria, Malate/aspart ate and alpha-glycerophosphate shuttle capacities were significantly increa sed in cardiac mitochondria from adult rats treated for 9 days with T3 comp ared to saline-treated controls, Liver mitochondria demonstrated a signific ant increase in alpha-glycerophosphate and no change in malate/aspartate sh uttle capacity, T3 increased steady state mRNA levels and activity of mitoc hondrial alpha-glycerophosphate dehydrogenase in both myocardium and liver. Quantitative immunoblot studies demonstrated a significant increase in asp artate-glutamate carrier levels in T3-treated myocardium suggesting a regul atory role of the aspartate/glutamate carrier in T3-treated hearts. Thyroid hormone effects on the NADH shuttles are tissue-specific. Changes in the N ADH shuttles in the presence of thyroid hormone excess occur both directly at the gene level and indirectly as an adaptive response. (C) 2000 Academic Press.