Mitochondrial binding of triiodothyronine (T3)

Abstract

To assess the distribution of the thyroid hormone triiodothyronine (T3) within intact living cells, freshly prepared dispersed rat hepatocytes were incubated with [125I]-T3 for periods of 5 min and 30 min. Light- and electron-microscopic (EM) radioautography was carried out to determine the distribution of grains over the isolated cells. Both procedures showed the grains distributed almost entirely over the cytoplasmic matrix rather than the nucleus. Grain counts under the EM were compared with expectation based on established quantitative methods. Only the mitochondria showed obvious and statistically significant grain counts, whereas the nucleus failed to accumulate grains in excess of expectations by chance alone based on area. The findings support the existence of mitochondrial binding of T3, presumably a prerequisite for its action in direct stimulation of the mitochondria.

Physiological Importance of the T3 Mitochondrial Pathway

“…Sterling's group provided the first evidence for the existence of mitochondrial T3 receptors. The organelle was shown to be a major T3 accumulation compartment 15 and specific T3 binding sites were described. 5 This latter result was confirmed by two other groups, 16,17 but other data concluded that the binding observed was not saturable.…”

Evidence for ADP‐ribosylation in the mechanism of rapid thyroid hormone control of mitochondria

“…A number of laboratories have shown that mitochondria acquire TX preferentially at very short times after administration in near-physiological amounts to thyroidectomised animals [2,4]. Saturable T3 binding sites with K, of 2 x 10-r' M-' have been reported in inner mitochondrial membranes from a number of tissues which respond to thyroid hormone (e.g.…”

“…Thyroid hormone has long been proposed to regulate mitochondrial metabolism and in recent years evidence has begun to accumulate that triiodothyronine (T3), in addition to proposed longer term effects exerted through transcription and translation, can elicit a very rapid direct response from mitochondria [l]. A number of laboratories have shown that mitochondria acquire TX preferentially at very short times after administration in near-physiological amounts to thyroidectomised animals [2,4]. Saturable T3 binding sites with K, of 2 x 10-r' M-' have been reported in inner mitochondrial membranes from a number of tissues which respond to thyroid hormone (e.g.…”

Thyroid hormone uptake into the cell and its subsequent localisation to the mitochondria

“…Using electron-microscopic radioautography following administration of ~zSI-T3 to isolated hepatocytes [22] the mitochondria were identified as the only obvious site of T3 accumulation during the first 30 min after administration. In another study injection of labelled T3 into thyroidectomised rats led to a rapid localisation of T3 to the mitochondria that then decreased over the next 3 h [23].…”