Transcription Regulates Biased Mitochondrial DNA Inheritance

Abstract

Maintaining mitochondrial DNA (mtDNA) is essential in eukaryotes for cellular respiration and ATP production by oxidative phosphorylation. Respiration is the preferred method for creating mitochondrial membrane potential, which is important for the import of nuclearly encoded proteins into the mitochondrion as well as supporting oxidative phosphorylation. Loss of mtDNA causes problems with maintaining membrane potential and mitochondrial ATP production, making mtDNA of critical importance to cells. However, mtDNA inheritance in proliferating cells is not fully understood. There is a set of mtDNA mutants in Saccharomyces cerevisiae, called hypersuppressives, that exhibit biased inheritance when competed with wild-type (rho+) mtDNA. A particular hypersuppressive allele, HS ORI5-1, damages rho+ mtDNA in the same cell and eliminates respiratory capability from progeny. Overexpression of a mitochondrial RNA exonuclease that interacts with the mitochondrial RNA polymerase inhibits mitochondrial transcription and restores inheritance of rho+ mtDNA when competed against HS ORI5-1. Reduction of mitochondrial transcription affects only particular hypersuppressive alleles, suggesting that there may be multiple ways to achieve biased inheritance.