A decline in the function of mitochondria may contribute to the aging process and age-related disorders. A functional decline could arise from accumulated mtDNA mutations over time, leading to reduced oxidative phosphorylation and other untoward effects on mitochondrial activities. Strategies that restore mitochondrial function could potentially offset key aspects of aging decline. RNA import into mammalian mitochondria is considered essential for replication, transcription, and translation of the mitochondrial genome but the pathway(s) and factors that control this import are poorly understood.
In recent studies we have shown a role for polynucleotide phosphorylase (PNPASE) in regulating the import of nuclear-encoded RNAs into the mitochondrial matrix. ... A mitochondrial RNA targeting signal was identified that enables the import of heterologous RNAs in a PNPASE-dependent manner. Combined, our studies show an unanticipated role for PNPASE in mediating the translocation of RNAs into mitochondria and provide a potential therapeutic route for halting or reversing the decline in mitochondrial function with aging.
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