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Expression of the rDNA-encoded mitochondrial protein Tar1p is stringently controlled and responds differentially to mitochondrial respiratory demand and dysfunction

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Abstract

The novel yeast protein Tar1p is encoded on the anti-sense strand of the multi-copy nuclear 25S rRNA gene, localizes to mitochondria, and partially suppresses the mitochondrial RNA polymerase mutant, rpo41-R129D. However, the function of Tar1p in mitochondria and how its expression is regulated are currently unknown. Here we report that Tar1p is subject to glucose repression and is up-regulated during post-diauxic shift in glucose medium and in glycerol medium, conditions requiring elevated mitochondrial respiration. However, Tar1p expression is down-regulated in response to mitochondrial dysfunction caused by the rpo41-R129D mutation or in strains lacking respiration. Furthermore, in contrast to the previously reported beneficial effects of moderate over-expression of Tar1p in the rpo41-R129D strain, higher-level over-expression exacerbates the ROS-derived phenotypes of this mutant, including decreased respiration and life span. Finally, two-hybrid screening and in vitro-binding studies revealed a physical interaction between Tar1p and Coq5p, an enzyme involved in synthesizing the mitochondrial electron carrier and antioxidant, coenzyme Q. We propose that Tar1p expression is induced under respiratory conditions to maintain oxidative phosphorylation capacity, but that its levels in mitochondria are typically low and stringently controlled. Furthermore, we speculate that Tar1p is down-regulated when respiration is defective to prevent deleterious ROS-dependent consequences of mitochondrial dysfunction.

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Acknowledgments

This work was supported by grant DAAD19-00-1-0650 from the Army Research Office. M.C-L. was supported by NIH Training grant GM07499-30. C.M.W. was a visiting student from the University of Bath when this work was performed. We wish to thank Dr. Michael Snyder for providing the Tar1p::LacZ reporter strain and the anti-Tar1p peptide antibody, Dr. Catherine Clarke for the Coq5p antibody, and Dr. William Studier for the bacterial Coq5p expression plasmid used in this study.

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Author notes

  1. Nicholas D. Bonawitz

    Present address: Department of Biochemistry, Purdue University, 175 South University Street, West Lafayette, IN, 47907-2063, USA

  2. Christopher M. Wearn

    Present address: Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK

Authors and Affiliations

  1. Department of Pathology and Genetics, Yale University School of Medicine, 310 Cedar Street, P.O. Box 208023, New Haven, CT, 06520-8023, USA

    Nicholas D. Bonawitz, Marc Chatenay-Lapointe & Gerald S. Shadel

  2. Graduate Program in Genetics and Molecular Biology, Emory University School of Medicine, Altanta, GA, USA

    Nicholas D. Bonawitz

  3. Graduate Program in Genetics, Yale University School of Medicine, New Haven, CT, USA

    Marc Chatenay-Lapointe

  4. Department of Biochemistry, Emory University School of Medicine, Rollins Research Center, Atlanta, GA, 30322, USA

    Christopher M. Wearn

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  1. Nicholas D. Bonawitz
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  2. Marc Chatenay-Lapointe
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  4. Gerald S. Shadel
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Corresponding author

Correspondence to Gerald S. Shadel.

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Communicated by R. Jensen.

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Bonawitz, N.D., Chatenay-Lapointe, M., Wearn, C.M. et al. Expression of the rDNA-encoded mitochondrial protein Tar1p is stringently controlled and responds differentially to mitochondrial respiratory demand and dysfunction. Curr Genet 54, 83–94 (2008). https://doi.org/10.1007/s00294-008-0203-0

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  • DOI: https://doi.org/10.1007/s00294-008-0203-0

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