PNPASE and RNA trafficking into mitochondria.

The mitochondrial genome encodes a very small fraction of the macromolecular components that are required to generate functional mitochondria. Therefore, most components are encoded within the nuclear genome and are imported into mitochondria from the cytosol. Understanding how mitochondria are assembled, function, and dysfunction in diseases requires detailed knowledge of mitochondrial import mechanisms and pathways. The import of nucleus-encoded RNAs is required for mitochondrial biogenesis and function, but unlike pre-protein import, the pathways and cellular machineries of RNA import are poorly defined, especially in mammals. Recent studies have shown that mammalian polynucleotide phosphorylase (PNPASE) localizes in the mitochondrial intermembrane space (IMS) to regulate the import of RNA. The identification of PNPASE as the first component of the RNA import pathway, along with a growing list of nucleus-encoded RNAs that are imported and newly developed assay systems for RNA import studies, suggest a unique opportunity is emerging to identify the factors and mechanisms that regulate RNA import into mammalian mitochondria. Here we summarize what is known in this fascinating area of mitochondrial biogenesis, identify areas that require further investigation, and speculate on the impact unraveling RNA import mechanisms and pathways will have for the field going forward. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.