Regulation of mitochondrial protein turnover by thyroid hormone(s)

Normal rats show levels of heart mitochondrial DNA and RNA (mit-DNA, mit-RNA) which are 0.66 and 18.82 µg/mg of mitochondrial proteins, or 0.15 and 4.35 fg/mitochondrion, respectively. Thyroidectomy reduces such values, while triiodothyronine (T₃) treatment effectively restores normal levels of mitochondrial nucleic acids. These findings complete the pattern obtained previously by the authors for the mitochondrial nucleic acids of liver and suggest that T₃ also increases the heart mitochondrial DNA and RNA content, probably due to stimulation of the respective mitochondrial polymerases.

Section: It Has Been Known For Many Years That Thysupporting

confidence: 92%

Effect of Thyroid Hormone on the Mitochondrial DNA and RNA Levels in Rat Cardiocytes

Meo¹,

Rosaroll²,

Leo³

1992

“…Therefore, the T 3 -induced decrease in the ability of mitochondria to withstand oxidative challenge could be one of the mechanisms responsible for the acceleration of the mitochondrial protein turnover by thyroid hormone [37,38]. If so, T 3 treatment should be associated with an altered distribution of the mitochondrial population into the three fractions, because the degradation processes should be greater in the M 1 fraction, exhibiting higher cytochrome content and lower antioxidant capacity.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant-Sensitive Triiodothyronine Effects on Characteristics of Rat Liver Mitochondrial Population

Venditti

Magistro

Masullo

et al. 1999

Whole mitochondrial population and three mitochondrial fractions were resolved by differential centrifugation from liver homogenates from euthyroid, hyperthyroid (ten daily i.p. injections of triiodothyronine (T₃), 10 μg/100 g body weight) and hyperthyroid vitamin E-treated (ten daily i.m. vitamin E injections, 20 mg/100 g body weight) rats. Homogenates and mitochondrial preparations were examined for their protein content, oxidative capacity, lipid peroxidation, antioxidant status, and susceptibility to oxidative stress. In all groups, antioxidant level was smaller and oxidative capacity, lipid peroxidation, and susceptibility to oxidants were greater in the heavy mitochondrial fraction. T₃ treatment was associated with increased oxidative capacity, lipid peroxidation, and susceptibility to oxidative stress, and decreased antioxidant levels in all preparations. It was also associated with increased mitochondrial protein content of homogenate and altered quantitative presence of the mitochondrial fractions. The vitamin E effects on the T₃-induced changes were different for the different parameters. Vitamin E did not modify the mitochondrial protein content in liver and oxidative capacity of the various preparations, reduced the changes in both susceptibility to oxidants and contribution of each fraction to the whole mitochondrial population, and reinstated euthyroid values for antioxidant capacity and lipid peroxidation. The incomplete recovery of euthyroid resistance to oxidants in vitamin E-treated rats is due to the vitamin inability to reinstate the levels of both antioxidants and hemoproteins, on which such a resistance depends. The vitamin E effect on the composition of the mitochondrial population is more difficult to explain, because of the complexity of the mechanisms underlying the mitochondrial population modulation by thyroid hormone. However, available data suggest that such a modulation occurs through changes in the turnover of the mitochondrial fractions to which an induction of mitochondrial protein synthesis and accelerated antioxidant-sensitive degradation contribute in different measure.

“…Parameters such as the total content of proteins [24], the turnover of whole mito chondria and their different protein compo nents [25], the mitochondrial respiration [8], the development of mitochondrial mem branes [26], the levels of mitochondrial en zymes [27,28] are differentially affected by thyroid hormone in different tissues. These results suggest that a physiological serum level of thyroid hormone is required to maintain ratios, between mitochondrial and other cel lular compartments or between different pro tein components of mitochondria, suitable for the tissue function.…”

Section: Discussionmentioning

confidence: 99%

Effect of Thyroid State on the Morphof unctional Properties of Heart Mitochondria

Meo¹,

Rosaroll²,

Leo³

1992

For an evaluation of the effect of thyroid hormone on the mitochondrial compartment of heart, we have studied morphological and functional characteristics of mitochondria within the heart of rats in different thyroid states. In particular, the relationship between membrane-bound proteins, such as the cytochromes, and the surface of inner mitochondrial membranes has been investigated. By quantitative electron microscopy it has been shown, according to our previous data, that thyroidectomy causes an increase in several parameters such as the specific mitochondrial mass (mg mitochondrial protein/g tissue), the number and inner membrane surface of mitochondria per unit volume of heart, without any significant variation of the ratio between the surface of the inner membranes and the volume of mitochondria. The treatment with substitutive doses of triiodothyronine (T₃) tends to restore the normal pattern. On the other hand, mitochondria isolated from thyroidectomized rats show lower oxygen consumption due to a lower content of cytochromes, which are distributed at lower density on the inner membranes. Also in this case the pattern is reversed by T₃ treatment. It is concluded that thyroid hormone causes an increase of mitochondrial cytochrome content, which, notwithstanding the decrease of the mitochondrial mass, leads to a higher respiratory rate and to a larger capacity of oxidative metabolism in the heart.