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Learn MorePolynucleotide phosphorylase (PNPase) is an essential mitochondria-localized exoribonuclease implicated in multiple biological processes and several human disorders. To reveal role(s) for PNPase in mitochondria, we established PNPase knockout (PKO) systems by first shifting culture conditions to enable cell growth with defective respiration. PKO resulted in loss of mitochondrial DNA (mtDNA) and a transcriptional profile similar to rho0 mtDNA deleted cells, with perturbations in cholesterol, lipid, and secondary alcohol metabolic pathways. PKO cells also showed growth and cell cycle profiles similar to rho0 cells. PKO in mouse inner ear hair cells cause progressive hearing loss that parallel human familial hearing loss previously linked to mutations in PNPase. Combined, our data suggest that mtDNA maintenance could provide a unifying connection for the large number of biological activities reported for PNPase. SOURCE: Fasih,Mubtasim,AhsanTeitell Lab, MRL 4-567 UCLA
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