Effects of thyroid hormones on oxidative phosphorylation

Harper, Mary‐Ellen; Ballantyne, James S.; Leach, Mark F.; Brand, Martin D.

doi:10.1042/bst0210785

Cited by 52 publications

(21 citation statements)

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“…10,46 In our comparison of proton leak kinetics for skeletal muscle mitochondria from rats made hyperthyroid and sham treated controls, proton leak at any given membrane potential is greater in mitochondria isolated from the hyperthyroid animals ( Figure 6). The result is consistent with the previous liver studies on isolated mitochondria and hepatocytes 14,15 and consistent with skeletal muscle being a target tissue for thyroid hormone. In addition, the presence of GDP did not affect the kinetics of the proton leak in rat skeletal muscle mitochondria ( Figure 6).…”

Section: Thyroid Hormonesupporting

confidence: 82%

“…It was shown that rats made hyperthyroid have increased proton leak at any given membrane potential when compared to sham treated controls whereas rats made hypothyroid have decreased proton leak compared to euthyroid controls. 14,15 Proton leak kinetics have been studied previously in rat skeletal muscle. 46 The pro®le of the proton leak rate as a function of membrane potential is typically non-ohmic and has been measured in whole rat hindquarter muscle and in isolated mitochondria.…”

Section: Thyroid Hormonementioning

confidence: 99%

“…Similarly, rats made hyperthyroid have an increased metabolic rate and have leakier liver mitochondria when compared to euthyroid controls. 14,15 Measurements on obese humans and animals show that they have increased resting metabolic rate when expressed per unit lean body mass compared to lean controls. 35,36 In a comparative study using obaob mice and lean controls, it was found that proton leak was greater in liver mitochondria from obese mice compared with those from lean mice (Figure 5a).…”

Section: Obesitymentioning

confidence: 99%

“…13 Similarly, rats made hyperthyroid have an increased metabolic rate and have leakier liver mitochondria when compared to euthyroid controls which in turn have leakier mitochondria than those from rats made hypothyroid. 14,15 In this paper we summarise recent work in our laboratory demonstrating the use of this indirect measurement of mitochondrial proton leak and how it has been applied to investigate inner membrane permeability to protons in (a) liver and (b) neuronal mitochondria from young and old rats, (c) liver mitochondria from lean and obese mice and (d) skeletal muscle mitochondria from rats made hyperthyroid. It is proposed that indirect measurement of mitochondrial proton leak is a convenient tool for investigating whether novel uncoupling proteins catalyse proton leak across the mitochondrial inner membrane.…”

Section: Introductionmentioning

confidence: 99%

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Indirect measurement of mitochondrial proton leak and its application

et al. 1999

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In mitochondria, ATP synthesis is coupled to oxygen consumption by the proton electrochemical gradient established across the mitochondrial inner membrane in a process termed oxidative phosphorylation. It has long been known from stoichiometric studies that ATP synthesis is not perfectly coupled to oxygen consumption. The major inef®ciency in the system is leakage of protons across the mitochondrial inner membrane driven by the proton electrochemical gradient. The kinetics of the proton leak can be determined indirectly, by measuring the oxygen consumption of mitochondria under non-phosphorylating conditions (plus oligomycin) as a function of the proton electrochemical gradient. This experimental system provides a convenient means to investigate inner membrane permeability to protons and the effect of factors that may effect that permeability. In this paper we review some results from our laboratory of indirect measurement of mitochondrial proton leak and how it has been applied to investigate the effect of aging, obesity and thyroid status on proton leak. The results show that (i) proton leak in isolated liver mitochondria is not signi®cantly different in a comparison of young and old rats, in contrast (ii) there is an apparent increase in proton leak in in situ mitochondria in hepatocytes from old rats when compared to those from young rats, (iii) proton leak in neuronal mitochondria in situ in synaptosomes is not signi®cantly different in young and old rats, (iv) proton leak is greater in isolated liver mitochondria from obaob mice compared to lean controls, (v) acute leptin (OB protein) administration restores the increased leak rate in isolated liver mitochondria from obaob mice to that of lean controls, (vi) administration of thyroid hormone (T 3 ) increases proton leak in rat muscle mitochondria, and (vii) proton leak in muscle mitochondria is insensitive to the presence of GDP. It is proposed that the experimental system described here for measuring proton leak, is an ideal functional assay for determining whether the novel uncoupling proteins increase inner membrane permeability to protons.

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Section: Thyroid Hormonesupporting

confidence: 82%

Section: Thyroid Hormonementioning

confidence: 99%

Section: Obesitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Indirect measurement of mitochondrial proton leak and its application

et al. 1999

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“…Thyroid hormone is well known to influence the metabolic rate of intact organisms; however, the distribution of the effect among various tissues is not as well understood. The liver is clearly established as an important mediator of the metabolic effects of thyroid hormone based on a series of studies utilizing hepatocytes isolated from rats with experimentally induced hypothyroidism or thyrotoxicosis (612), reviewed by Harper and Brand (613). Hepatocyte oxygen consumption was positively correlated with thyroid hormone status of the animal; analysis of respiration indicates that basal mitochondrial proton leak is also positively correlated with oxygen consumption (614).…”

Section: And Recommendation 55amentioning

confidence: 99%