Specific binding sites for 3,3′‐diiodo‐l‐thyronine (3,3′‐T₂) in rat liver mitochondria

Abstract

Specific binding sites for 3,3'-T2 can be detected in swollen and osmotically treated mitochondria (OTM) from normal and hypothyroid rat liver. In hypothyroid animals, maximal values of binding were obtained at 0°C and 20°C while values were lower at 37°C and no specific binding could be observed at 60°C. Binding was maximal at pH 6.4 and the mean values for the apparent association constant (Ka) and the binding capacity were on average 0.5 x 108 M -~ and 2.4 pmol/mg mitochondrial protein, respectively. No differences were observed between normal and hypothyroid rats with the exception of the capacity that was higher in normal animals (5.5 pmol/mg mitochondrial protein). The specificity of 3,3'-T2 binding, examined in competition studies, followed this order: 3,3'-T2 > 3,5-T 2 > rT3. The other iodothyronines (3',5'-T2, T3, T4, 3-T~, 3'-T~, 3,5-Diac and 3,3'-Diac) showed only a small competition or none at all.

Involvement of the L-Type Amino Acid Transporter Lat2 in the Transport of 3,3′-Diiodothyronine across the Plasma Membrane

“…cell metabolism. For example, 3,3′-T 2 binding sites were discovered in rat mitochondria, suggesting a role in metabolic regulation of the cell [25]. Also, stimulation of the cytochrome oxygenase was noted, but this data has not yet been independently confirmed.…”

Computational Prediction and in Vitro Analysis of Potential Physiological Ligands of the Bile Acid Binding Site in Cytochrome c Oxidase

“…Thyroid hormones, including T3, have been shown to stimulate metabolism, 58 to interact specifically with intact mitochondria, 54,59,60 and to alter C c O activity. 61,62 Retinoic acid, the degradative product of the essential vitamin A, has been tied to mitochondrial functions including transcriptional regulation, thermogenesis, and apoptosis.…”

Characterization of the binding of 3,3′-di-iodo-l-thyronine to rat liver mitochondria

“…We have recently shown (Goglia et al 1994 >) that T2s interact rapidly with the isolated COX complex. Such an inter¬ action leads to conformational changes and to the stimu¬ lation of enzymatic activity.…”

“…In a previous paper, we reported that binding capacity was higher in euthyroid than in hypothyroid rats (Lanni et al 1994/)) indicating that the number of binding sites, like some components of the electron transport chain, is affected by T3. In the light of that finding, the lower binding capacity seen in hyperthyroid rats in the present study might seem to be a discrepancy, but it could be the consequence of a high endogenous occupancy of the binding sites in the hyperthyroid state.…”

“…These results, together with the evidence of the rapid effects of T2s on energy metabolism, led us to suggest a direct interaction of T2s with mitochondria. In particular, results showing that T2s can stimulate the activity of the cytochrome oxidase (COX) complex isolated from bovine heart mitochondria, and change its visible spectrum, led us to suggest that they alter the kinetic properties of the enzyme by interacting with its non-catalytic subunits (Goglia et al 1994/)). However, use of a Scatchard analysis of the binding of T2s with isolated COX complexes, designed to show the presence of specific binding sites for T2s, has given negative results so far (authors' unpublished data).…”