Regulation of adenine nucleotide translocase and glycerol 3-phosphate dehydrogenase expression by thyroid hormones in different rat tissues

Abstract

Thyroid hormone (T $ )-dependent gene expression of the adenine nucleotide translocase (ANT) and the FAD-linked glycerol 3-phosphate dehydrogenase (mGPDH) was investigated in several rat tissues. Both proteins provide an important link between cytosolic and mitochondrial metabolic pathways and seem to be involved in the stimulation of mitochondrial oxygen consumption in response to T $ . Here we show that two ANT isoforms are expressed in rat, the muscle-specific ANT1 form and the ubiquitous ANT2 form. The expression of ANT1 mRNA is not sensitive to T $ whereas the amount of ANT2 mRNA is increased 7-9-fold in liver and heart within 12-48 h after T $ application. Little or no effect of T $ on ANT2 mRNA was observed in kidney and brain. The mRNA changes are paralleled by an increase in ANT protein, thus explaining the accelerated ADP\ATP exchange observed in mitochondria isolated from hyperthyroid rats. The key role of ANT2 in the control of hyperthyroid

Hepatic gene expression patterns in thyroid hormone-treated hypothyroid rats

“…Among the T3-responsive genes, which we have identified in our study, several genes have already been described to be T3 regulated, e.g. ANT2, myelin basic protein, ATP synthase subunit or apolipoprotein AIV (Dümmler et al 1996, Miller et al 2001, Clement et al 2002, Flores-Morales et al 2002. Thus, our screening protocol was successful in identifying differentially T3-regulated genes.…”

“…However, several T3-target genes are expressed 'late' (24-48 h) after the administration of T3 in vivo, including cytochrome c (Scarpulla et al 1986) and adenine nucleotide translocator 2 (ANT2) (Dümmler et al 1996) and, noteworthy, an interaction of TR (via a TRE) with these target genes has not been observed , Weitzel et al 2003. These observations suggest an induction mechanism via the activation of an intermediate factor (s).…”

A Refined Analysis of Superoxide Production by Mitochondrial sn-Glycerol 3-Phosphate Dehydrogenase

“…Expression and activity of mGPDH are known to differ widely between different tissues and in different environmental and hormonal states (Fig. 4, a and b) (3,(5)(6)(7). Therefore, depending on metabolic conditions, mGPDH not only coordinates cellular energy production but also probably participates in oxidative signaling both within mitochondria and beyond.…”

“…This shuttle activity is thought to coordinate glycolytic and mitochondrial metabolism in highly active tissues, and fittingly, mGPDH shows the highest expression in thermogenic brown fat, type II skeletal muscle fibers, brain, sperm, and pancreatic beta cells (2)(3)(4). Tissues with characteristically low expression of mGPDH, such as liver, kidney, and heart, show increased enzyme activity in response to thyroid and steroid hormones, whereas those with high expression are generally insensitive to this regulation (3,(5)(6)(7). Variations in mGPDH expression, activity, or genetic sequence have been associated with increased plasma levels of glycerol and free fatty acids (8), mental retardation (9), cancers (5, 10 -12), and diabetes (13,14).…”

Thyroid hormone regulation of cardiac bioenergetics: role of intracellular creatine

“…These thyroid hormone (T 3 )-induced alterations are associated with increased expression and activity of adenine nucleotide translocase (isoform 2) without a consistent change in cytosolic or mitochondrial creatine (Cr) kinase protein (5,10,13). Despite the positive inotropic and chronotropic effects of thyroid hormone on the heart that are accompanied with increased expression of mitochondrial and contractile proteins and membrane-bound enzymes, including Na-K ϩ -ATPase and Ca-ATPase, the hyperthyroid heart exhibits a decrease (not an increase) in its capacity to perform work at a maximal level (5,10,30,46).…”