This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long term goal of this project is to understand the mechanisms involved in mitochondrial DNA (mtDNA) maintenance. The overall goal of the present phase is to determine the role played by YGR150c in the preservation of mtDNA. Mitochondrial dysfunction has been long implicated in a number of age-related pathologies, cancer and diabetes. One of the reasons for mitochondrial failure is the damage to, and/or partial or total loss of mtDNA. The loss of the mtDNA renders the cell unable to perform aerobic respiration. mtDNA depletion syndromes (MDS) are a heterogeneous group of severe mitochondrial disorders of infancy and childhood, characterized by a profound reduction in mtDNA copy number. MDS is considered a prevalent cause of multiple respiratory chain deficiency in pediatric patients. However, current genetic screenings relate only to genes involved in maintaining the dNTP pool in mitochondria and explain only 10 % of the cases. The integrity of mtDNA is mainly maintained by nuclear gene products. However, many of the mechanisms that contribute to the preservation of mtDNA are still unclear or unknown. Saccharomyces cerevisiae is an ideal organism with which to study mitochondrial function because it can live without this organelle.