DIFFERENTIAL EXPRESSION OF MITOCHONDRIAL-DNA REPLICATION FACTORS IN MAMMALIAN-TISSUES

Mitochondrial biogenesis and mitochondrial DNA (mtDNA) replication are regulated during development and in response to physiological stresse s, but the regulatory events that control the abundance of mtDNA in ce lls of higher eukaryotes have not been defined at a molecular level, I n this study, we observed that expression of the catalytic subunit of DNA polymerase gamma (POL gamma(CAT)) mRNA varies little among differe nt tissues and is not increased by continuous neural activation of ske letal muscle, a potent stimulus to mitochondrial bio genesis, Increase d copy number for the POL gamma locus in a human cell line bearing a p artial duplication of chromosome 15 increased the abundance of POL gam ma(CAT) mRNA without up-regulation of mtDNA, In contrast, expression o f mitochondrial single-stranded DNA-binding (mtSSB) mRNA is regulated coordinately with variations in the abundance of mtDNA among tissues o f mammalian organisms and is up-regulated in association with the enha nced mitochondrial biogenesis that characterizes early postnatal devel opment of the heart and the adaptive response of skeletal myofibers to motor nerve stimulation, In addition, we noted that expression of mtS SB is concentrated within perinuclear mitochondria that constitute act ive sites of mtDNA replication, We conclude that constitutive expressi on of the gene encoding the catalytic subunit of mitochondrial DNA pol ymerase is sufficient to support physiological variations in mtDNA rep lication among specialized cell types, whereas expression of the mtSSB gene is controlled by molecular mechanisms acting to regulate mtDNA r eplication or stability in mammalian cells.