title: Thyroid hormone modifies mitochondrial phenotype by increasing protein import without altering degradation.
abstract: The mitochondrial phenotype within cardiac muscle cells is dramatically altered by thyroid hormone. We report here that this can be accounted for, in part, by modifications in the rate of mitochondrial protein import. The import of matrix-localized precursor proteins malate dehydrogenase (MDH) and ornithine carbamoyltransferase was augmented, whereas the insertion of the outer membrane protein Bcl-2 was unaffected by thyroid hormone treatment. Coincident with increases in the import of these matrix-localized precursors were thyroid hormone-induced elevations in the outer membrane receptor Tom20 and the matrix heat-shock protein mthsp70. The phospholipid cardiolipin was not involved in mediating the thyroid hormone-induced increase in import, as judged from adriamycin inhibition studies. When the import reaction was supplemented with rat heart cytosol, we found that 1) MDH import was stimulated, but Bcl-2 import was inhibited and 2) thyroid hormone did not influence the effect of the cytosol on import rates. Thus distinct requirements exist for the mitochondrial import of precursor proteins, destined for different organellar compartments. Although import of these matrix-localized proteins was augmented by thyroid hormone treatment, the proteolysis of matrix proteins was unaffected as indicated by the degradation of cytob2(167)RIC-dihydrofolate reductase, a chimeric protein missorted to the matrix. Thus our data indicate that at least some thyroid hormone-induced modifications of the mitochondrial phenotype occur due to the compartment-specific upregulation of precursor protein import rates, likely mediated via changes in the expression of protein import machinery components.
authors.affiliation: Departments of Biology and Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada M3J 1P3.
authors.forename: E E
authors.initials: EE
authors.lastname: Craig
authors.forename: A
authors.initials: A
authors.lastname: Chesley
authors.forename: D A
authors.initials: DA
authors.lastname: Hood
mesh_terms: D048948:14-3-3 Proteins; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002308:Cardiolipins / Q000502:physiology; D003600:Cytosol / Q000378:metabolism / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D007267:Injections; D007425:Intracellular Membranes / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018832:Molecular Chaperones / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D010641:Phenotype; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D000099221:Protein Kinase C zeta
chemical_list: D048948:14-3-3 Proteins; D002308:Cardiolipins; D008291:Malate Dehydrogenase; D018832:Molecular Chaperones; D009124:Muscle Proteins; D011498:Protein Precursors; D013762:Tetrahydrofolate Dehydrogenase; D014284:Triiodothyronine; C490392:Prkcz protein, rat; D000099221:Protein Kinase C zeta; C490391:Ywhaz protein, rat; C090759:mitochondrial import stimulation factor, rat