Global transcriptional response of Saccharomyces cerevisiae to the deletion of SDH3

Although the Sdhp has no direct role in transcriptional regulation and the flux through the corresponding reaction under the studied conditions is very low, deletion of SDH3 resulted in significant changes in the expression of several genes involved in various cellular processes ranging from metabolism to the cell-cycle. By using various bioinformatics tools we explored the organization of these transcriptional changes in the metabolic and other cellular functional interaction networks.Our results show that the transcriptional regulatory response resulting from the impaired respiratory function is linked to several different parts of the metabolism, including fatty acid and sterol metabolism.Mitochondrial respiration plays a central role in energy metabolism in eukaryotic cells. It is involved in generating energy, primarily in the form of ATP, upon oxidation of different carbon sources such as ethanol, pyruvate and diverse organic acids. This functionality is conserved across all eukaryotic cells. Consequently, metabolic and regulatory mechanisms governing the mitochondrial energy generation have many implications for the functioning of the cell as a whole. A primary component of mitochondrial metabolism is the TCA cycle which apart from producing NADH needed in the oxidative phosphorylation also supplies precursors for biomass synthesis, e.g. 2-oxoglutarate and oxaloacetate. The coupling between metabolism and oxidative phosphorylation is also reflected in the tight transcriptional regulation of the TCA cycle, for example, as observed in Saccharomyces cerevisiae during the diauxic shift between fermentative and oxidative metabolism. The TCA cycle is also known to be transcriptionally regulated in response to oxygen and carbon substrate concentrations. The succinate dehydrogenase complex (Sdhp) serves as a link between the TCA cycle and electron transport chain. Specifically, FADH2 produced during oxidation of succinate to fumarate acts as an electron donor for ubi