[Frontiers in Bioscience 17, 1079-1093, January 1, 2012]

Mitochondrial and nuclear genomic integrity after oxidative damage in Saccharomyces cerevisiae

Oya Yazgan1, Jocelyn E. Krebs1

1University of Alaska Anchorage, Alaska 99508, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Genomic architecture of Saccharomyces cerevisiae
3.1. The nuclear genome
3.2. The mitochondrial genome
3.3. Nuclear and mitochondrial communication
4. Cellular oxidative damage
5. Consequences of oxidative damage to the genome
5.1. Some of the mitochondrial and nuclear DNA repair components overlap
5.2. Increased ROS cause mitochondrial genomic instability
5.3. Mitochondrial DNA loss leads to nuclear genomic instability
5.4. Effects of oxidative damage to the nuclear genome
6. Concluding remarks
7. Acknowledgements
8. References

1. ABSTRACT

All cells have the ability to adjust their metabolism to their changing environment to be able to survive. This adaptation is coordinated by various systems in the cell and mitochondria seem to play a unique and important role. Most endogenous oxidative damage to cells is actually generated as a byproduct of the mitochondrial function, which in turn damages mitochondrial structures more extensively due to their proximity to the source. Excessive damage to mitochondria leads to loss of parts or all of mtDNA, but unlike other organisms, S. cerevisiae cells are able to survive without mtDNA or respiration when grown on fermentative carbon sources. This allows studies of the role of mitochondria in the maintenance of cellular integrity, since lack of mitochondrial DNA frequently leads to genomic instability. Mitochondria are known for their role in respiration, ATP production and apoptosis, but it is now becoming clear that their function is intimately connected to diverse processes such as calcium and iron homeostasis and amino acid metabolism, and thus their dysfunction is not well tolerated. In this review, we discuss the mechanisms by which mitochondrial dysfunction can lead to genomic instability and the effect of the carbon source on this process.