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Molecular and Cellular Biology, January 1999, p. 657-670, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Direct Regulation of Mitochondrial RNA Synthesis by Thyroid Hormone

José A. Enríquez,* Patricio Fernández-Silva, Nuria Garrido-Pérez, Manuel J. López-Pérez, Acisclo Pérez-Martos, and Julio Montoya*

Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, E-50013 Zaragoza, Spain

Received 18 June 1998/Returned for modification 27 July 1998/Accepted 15 September 1998

We have analyzed the influence of in vivo treatment and in vitro addition of thyroid hormone on in organello mitochondrial DNA (mtDNA) transcription and, in parallel, on the in organello footprinting patterns at the mtDNA regions involved in the regulation of transcription. We found that thyroid hormone modulates mitochondrial RNA levels and the mRNA/rRNA ratio by influencing the transcriptional rate. In addition, we found conspicuous differences between the mtDNA dimethyl sulfate footprinting patterns of mitochondria derived from euthyroid and hypothyroid rats at the transcription initiation sites but not at the mitochondrial transcription termination factor (mTERF) binding region. Furthermore, direct addition of thyroid hormone to the incubation medium of mitochondria isolated from hypothyroid rats restored the mRNA/rRNA ratio found in euthyroid rats as well as the mtDNA footprinting patterns at the transcription initiation area. Therefore, we conclude that the regulatory effect of thyroid hormone on mitochondrial transcription is partially exerted by a direct influence of the hormone on the mitochondrial transcription machinery. Particularly, the influence on the mRNA/rRNA ratio is achieved by selective modulation of the alternative H-strand transcription initiation sites and does not require the previous activation of nuclear genes. These results provide the first functional demonstration that regulatory signals, such as thyroid hormone, that modify the expression of nuclear genes can also act as primary signals for the transcriptional apparatus of mitochondria.

* Corresponding author. Mailing address: Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, E-50013 Zaragoza, Spain. Phone for José A. Enríquez: 34-976761646. Phone for Julio Montoya: 34-976761640. Fax: 34-976761612. E-mail for José A. Enríquez: enriquez{at}posta.unizar.es. E-mail for Julio Montoya: jmontoya{at}posta.unizar.es.

Molecular and Cellular Biology, January 1999, p. 657-670, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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