Intersections of distinct biological pathways in cells allow for nodes of metabolic regulation. This work describes the discovery of the intersection of two pathways in yeast mitochondria: RNA processing and fatty acid synthesis and attachment. Analysis of the components of the pathways is presented here along with a model illustrating the connection as a potential mode of regulation of mitochondrial gene expression.A genome-wide screen of respiratory-deficient <italic>Saccharomyces cerevisiae</italic> deletion strains for defects in mitochondrial RNA processing revealed that two novel genes affect processing of mitochondrial tRNAs by RNase P. One gene encodes Htd2, an enzyme in the type II mitochondrial fatty acid synthesis pathway (FAS II). The other gene is described here as encoding Lip3, an enzyme involved in the synthesis and attachment of the co-factor lipoic acid, which is synthesized from a product of the FAS II pathway.RPM1 is the mitochondrial-encoded RNA subunit of mitochondrial RNase P. The multigenic transcription unit containing RPM1 also contains tRNA<super>pro</super>. Maturation of RPM1 necessitates processing of the tRNA by RNase P. Thus, RNase P is required for maturation of its own RNA component, constituting a positive feedback cycle. The present work demonstrates that a product of the FAS II pathway is necessary for the assembly or activity of RNase P, as deletion of any gene encoding an FAS II enzyme results in inefficient processing of tRNApro from the transcript.Analysis of the enzymes involved in the synthesis and attachment of lipoic acid to target proteins is also described here. Disruption of any of these enzymes affects protein lipoylation and tRNA processing. Gcv3, a target of lipoylation, was found to be required for lipoylation as well as for efficient tRNA processing.A second feedback cycle controlling pyruvate dehydrogenase activity and fatty acid synthesis may be functional under certain conditions. Pyruvate dehydrogenase, which provides acetyl-CoA for the FAS II pathway, requires lipoic acid for its activity. It is hypothesized that the two feedback cycles and the role of Gcv3 may provide switch-like regulation of mitochondrial gene expression in response to the nutritional state of the cell.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/194674 |
| Date | January 2008 |
| Creators | Schonauer, Melissa |
| Contributors | Dieckmann, Carol L., Dieckmann, Carol L., Tax, Frans, Weinert, Ted |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Electronic Dissertation |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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