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Molecular and Cellular Biology, February 2000, p. 805-815, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Tight Control of Respiration by NADH Dehydrogenase ND5 Subunit Gene Expression in Mouse Mitochondria

Yidong Bai, Rebecca M. Shakeley, and Giuseppe Attardi*

Division of Biology, California Institute of Technology, Pasadena, California 91125

Received 7 June 1999/Returned for modification 3 September 1999/Accepted 24 October 1999

A mouse cell variant carrying in heteroplasmic form a nonsense mutation in the mitochondrial DNA-encoded ND5 subunit of the respiratory NADH dehydrogenase has been isolated and characterized. The derivation from this mutant of a large number of cell lines containing between 4 and 100% of the normal number of wild-type ND5 genes has allowed an analysis of the genetic and functional thresholds operating in mouse mitochondria. In wild-type cells, ~40% of the ND5 mRNA level was in excess of that required for ND5 subunit synthesis. However, in heteroplasmic cells, the functional mRNA level decreased in proportion to the number of wild-type ND5 genes over a 25-fold range, pointing to the lack of any compensatory increase in rate of transcription and/or stability of mRNA. Most strikingly, the highest ND5 synthesis rate was just sufficient to support the maximum NADH dehydrogenase-dependent respiration rate, with no upregulation of translation occurring with decreasing wild-type mRNA levels. These results indicate that, despite the large excess of genetic potential of the mammalian mitochondrial genome, respiration is tightly regulated by ND5 gene expression.

* Corresponding author. Mailing address: Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125. Phone: (626) 395-4930. Fax: (626) 449-0756. E-mail: attardig{at}seqaxp.bio.caltech.edu.

Molecular and Cellular Biology, February 2000, p. 805-815, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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