RNA Technologies for Mitochondrial Genetics

Abstract

Mitochondria ensure fundamental functions in eukaryotic cells. They possess their own genetic system that provides a number of essential polypeptides of the oxidative phosphorylation chain. As a consequence, the respiratory complexes are built from both nuclear-encoded and organellar-encoded subunits. Mitochondrial biogenesis and response to the energetic or metabolic demands of the cell thus relies on elaborate regulation networks and continuous cross talk with the nucleus, as well as with plastids in plants. Main questions remain open regarding these control mechanisms and their relation with the complex transcriptional and posttranscriptional processes that take place in mitochondria. In particular, the field of organelle noncoding RNAs is growing and points to an involvement of mitochondria in cellular RNA interference. To gain further knowledge, manipulating the organelle genetic system is the obvious way to go, but mitochondrial transformation remains restricted to a couple of unicellular organisms. The scientific challenge is of wide relevance, as mutations or rearrangements in the mitochondrial genome cause incurable neurodegenerative diseases in human or lead to cytoplasmic male sterility in plants. RNA technologies may provide another path, as mitochondria naturally import several types of RNA, depending on the organism. Exploiting the natural mechanisms to target customized RNAs to or into mitochondria has begun. Considering their high specificity versus interfering RNAs, catalytic RNAs are of particular interest for such strategies. Major breakthrough has already been obtained in silencing mitochondrial RNAs through the import of trans-cleaving hammerhead ribozymes.