UCSF

Mitochondria carry their own genome (mtDNA), which is present in multiple copies in all eukaryotic cells. Copy number of mtDNA in each cell is tightly maintained, yet surprisingly the cellular mechanisms that regulate mtDNA copy number remain poorly understood. To address this question, we carried out a forward genetic screen in the budding yeast S. cerevisiae and identified mutants exhibiting altered mtDNA levels. This screen revealed a previously uncharacterized mitochondrial gene, Mrx6, whose deletion results in a marked increase of mtDNA without affecting mitochondrial structure or cell size. We found that Mrx6 forms a complex with a sequence-related protein, Pet20, with Mam33, and with the conserved Lon protease Pim1, which is important for mitochondrial protein quality control. Furthermore, the Mrx6 complex colocalizes with mtDNA. Because human and bacterial Lon proteases have been proposed to regulate DNA replication by degrading replication initiation factors, our results suggest that the Mrx6 complex may similarly control mtDNA levels through degradation of key proteins regulating mtDNA replication.