Photothermal Nanoblade and Nucleic Acid Import into Mitochondria: Can We Improve Bioenergetics for People?

Numerous diseases result from mutations within the mitochondrial genome. A functional decline due to mtDNA mutations could lead to reduced oxidative phosphorylation and other untoward effects on mitochondrial activities. Strategies that restore mitochondrial function could potentially diminish the ill effects of mitochondrial-driven diseases. In this presentation we will discuss two strategies for repairing mtDNA mutations. In one approach we are developing a photothermal nanoblade to introduce whole mitochondria containing functional mtDNA into cells. In a second approach, we consider targeted mitochondrial import of corrective ribonucleic acid (RNA) to compensate for mtDNA mutations. 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. Previously, polynucleotide phosphorylase (PNPASE) was localized in the mitochondrial intermembrane space, a location lacking resident RNAs. In recent studies we have shown a role for PNPASE in regulating the import of nuclear-encoded RNAs into the mitochondrial matrix. These recent 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 in human disease.