Adaptive expression responses in the Pol-γ null strain of S. pombe depleted of mitochondrial genome

We show that disruption of the nuclear gene pog1+ that encodes Pol-γ is sufficient to deplete mtDNA in S. pombe. Cells bearing pog1Δ allele require substantial growth periods to form petite colonies. Mitotracker assays indicate that pog1Δ cells are defective in mitochondrial function and EM analyses suggest that pog1Δ cells lack normal mitochondrial structures. Depletion of mtDNA in pog1Δ cells is evident from quantitative real-time PCR assays. Genome-wide expression profiles of pog1Δ and other mtDNA-less cells reveal that many genes involved in response to stimulus, energy derivation by oxidation of organic compounds, cellular carbohydrate metabolism, and energy reserve metabolism are induced. Conversely, many genes encoding proteins involved in amino acid metabolism and oxidative phosphorylation are repressed.By showing that Pol-γ is essential for mtDNA maintenance and disruption of pog1+ alters the genome-wide expression profiles, we demonstrated that cells lacking mtDNA exhibit adaptive nuclear gene expression responses in the petite-negative S. pombe.Mitochondria are essential organelles that generate ATP through the respiratory chain to provide energy for many biochemical reactions and cellular processes in eukaryotic cells. Mitochondria are one of the organelles that contain its own genetic material, the mitochondrial genome (mtDNA). It is thought that mitochondria evolved over millions of years after originating from bacteria that had invaded eukaryotic cells. It is thus not surprising that Pol-γ has a lineage similar to prokaryotic DNA polymerase A in E. coli [1,2]. A nuclear-DNA encoded gene of the catalytic subunit of Pol γ (POLG1 in human and MIP1 in Saccharomyces cerevisiae) has been shown to be essential for mtDNA stability [3,4].The mitochondrial genomes in many mammalian systems are small when compared to their corresponding nuclear genomes. Human mtDNA, for example, is only ~16.6 kb in length and rodent mtDNA is ~16.3 kb [5-9]. Mutations in either h