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Thyroid hormone action: the mitochondrial pathway.

K Sterling, P O Milch, M A Brenner

    Science (New York, N.Y.)
    |September 2, 1977
    PubMed
    Summary
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    Researchers identified specific thyroid hormone binding proteins in rat tissues, particularly in mitochondria. This suggests thyroid hormones may directly impact mitochondrial function, influencing energy production.

    Area of Science:

    • Biochemistry
    • Cell Biology
    • Endocrinology

    Background:

    • Thyroid hormones, triiodothyronine and thyroxine, are crucial for metabolism.
    • Their precise subcellular mechanisms of action, especially at the mitochondrial level, require further elucidation.

    Purpose of the Study:

    • To investigate the presence and characteristics of thyroid hormone binding proteins across various subcellular compartments in rat tissues.
    • To determine if mitochondria possess specific receptors for thyroid hormones and assess the functional implications.

    Main Methods:

    • Subcellular fractionation of rat liver and kidney tissues.
    • Analysis of protein binding affinities for triiodothyronine and thyroxine using association constants.
    • Testing binding specificity with hormone analogs and stereoisomers.

    Related Experiment Videos

  • Assessing mitochondrial oxidative phosphorylation in response to triiodothyronine.

    • Main Results:

    • Specific thyroid hormone binding proteins were identified in cytosol, nuclei, and mitochondria.
    • The highest affinity binding protein was located in the inner mitochondrial membrane.
    • Mitochondrial membranes from responsive tissues (liver, kidney, muscle) contained saturable receptors, unlike unresponsive tissues (brain, spleen, testis).
    • Triiodothyronine enhanced oxidative phosphorylation in mitochondria from hypothyroid rats.

    Conclusions:

    • Thyroid hormones bind to specific proteins within multiple subcellular compartments, including mitochondria.
    • Mitochondria possess high-affinity, stereospecific receptors for thyroid hormones, suggesting a direct role in hormone action.
    • Thyroid hormones directly influence mitochondrial function, impacting oxidative phosphorylation and energy metabolism.