The trifunctional protein mediates thyroid hormone receptor-dependent stimulation of mitochondria metabolism.

Molecular Endocrinology
E Sandra ChocronJames D Lechleiter

Abstract

We previously demonstrated that the thyroid hormone, T(3), acutely stimulates mitochondrial metabolism in a thyroid hormone receptor (TR)-dependent manner. T(3) has also recently been shown to stimulate mitochondrial fatty acid oxidation (FAO). Here we report that TR-dependent stimulation of metabolism is mediated by the mitochondrial trifunctional protein (MTP), the enzyme responsible for long-chain FAO. Stimulation of FAO was significant in cells that expressed a nonnuclear amino terminus shortened TR isoform (sTR(43)) but not in adult fibroblasts cultured from mice deficient in both TRα and TRβ isoforms (TRα(-/-)β(-/-)). Mouse embryonic fibroblasts deficient in MTP (MTP(-/-)) did not support T(3)-stimulated FAO. Inhibition of fatty-acid trafficking into mitochondria using the AMP-activated protein kinase inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine (compound C) or the carnitine palmitoyltransferase 1 inhibitor etomoxir prevented T(3)-stimulated FAO. However, T(3) treatment could increase FAO when AMP-activated protein kinase was maximally activated, indicating an alternate mechanism of T(3)-stimulated FAO exists, even when trafficking is presumably high. MTPα protein levels and...Continue Reading

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Citations

Mar 5, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·AlberTinka J MurkArno C Gutleb
Feb 14, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Naomi L SayreJames D Lechleiter
Oct 31, 2015·Scientific Reports·Michele TavecchioDario C Altieri
Sep 9, 2015·Scientific Reports·Woo-Sung KwonMyung-Geol Pang
Feb 24, 2019·International Journal of Molecular Sciences·Mitsuhiro MoritaMami Noda
Aug 8, 2019·Thyroid : Official Journal of the American Thyroid Association·Rohit A SinhaPaul M Yen
Sep 3, 2021·Biochemical and Biophysical Research Communications·Wesley Wang, Dolena Ledee

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