This Article Full Text Full Text (PDF) All Versions of this Article: 146/5/2462    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yehuda-Shnaidman, E. Articles by Bar-Tana, J. Search for Related Content PubMed PubMed Citation Articles by Yehuda-Shnaidman, E. Articles by Bar-Tana, J.

Modulation of Mitochondrial Transition Pore Components by Thyroid Hormone

Department of Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem 91120, Israel

Address all correspondence and requests for reprints to: Dr. Jacob Bar-Tana, Department of Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem 91120, Israel. E-mail: bartanaj{at}cc.huji.ac.il.

Thyroid hormone (TH) modulates metabolic efficiency by controlling the coupling of mitochondrial oxidative phosphorylation. However, its uncoupling mode of action is still enigmatic. Treatment of Jurkat or GH₃ cells with T₃ is reported here to result in limited, Cyclosporin A-sensitive mitochondrial depolarization, conforming to low conductance gating of the mitochondrial transition pore (MTP). MTP protein components induced by T₃ treatment were verified in T₃-treated and hypothyroid rat liver as well as in Jurkat cells. T₃ treatment resulted in increase in mitochondrial Bax and Bak together with decreased mitochondrial Bcl2. T₃-induced mitochondrial depolarization was aborted by overexpression of Bcl2. In contrast to Bax-Bcl2 family proteins, some other MTP components were either not induced by T₃ (e.g. voltage-dependent anion channel) or were induced, but were not involved in Cyclosporin A-sensitive MTP gating (e.g. Cyclophilin D and adenine nucleotide translocase-2) Hence, TH-induced mitochondrial uncoupling may be ascribed to low conductance MTP gating mediated by TH-induced increase in mitochondrial proapoptotic combined with a decrease in mitochondrial antiapoptotic proteins of the Bax-Bcl2 family.

This article has been cited by other articles:

				L. Siculella, S. Sabetta, A. M. Giudetti, and G. V. Gnoni Hypothyroidism Reduces Tricarboxylate Carrier Activity and Expression in Rat Liver Mitochondria by Reducing Nuclear Transcription Rate and Splicing Efficiency J. Biol. Chem., July 14, 2006; 281(28): 19072 - 19080. [Abstract] [Full Text] [PDF]