The transfer of nucleic
acids from organelles to the nucleus has influenced the evolution of
eucaryotes, the structure of chromosomes, and cellular pathology. In
S. cerevisiae, mutations in genes involved in at least three
aspects of mitochondrial biology can influence the rate of mtDNA
escape to the nucleus. First, inactivation of Yme1p, a metal-dependant
protease located in the inner mitochondrial membrane, leads to damaged
mitochondrial compartments that are turned over by the vacuole with
the subsequent release of mtDNA. Second, mutations in MMM1 and
YME4 lead to alterations of mitochondrial morphology and an
associated increase in the escape of mtDNA. Mmm1p is necessary for
proper maintenance of mitochondrial morphology, apparently via
association with the actin cytoskeleton. Suppressors of mmm1
deletions that restore to various degrees wild type mitochondrial
morphology also suppress the mtDNA loss phenotype. Third, genes
involved in packaging mtDNA into membrane associated nucleoids can
also influence the rate of mtDNA escape. Yme2p is found in the inner
mitochondrial membrane and co-purifies with both mtDNA and the
nucleoid associated protein Abf2p. YME2 deletion strains
display only a high rate of mtDNA escape whereas yme2-4 strains
have several severe growth defects and no escape of mtDNA. Based on
the genetic, physical, and sequence properties of Yme2p, we propose
that this protein is involved in several mtDNA transactions.
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