Abstract
BackgroundMitochondrial respiration is an important and widely conserved cellular function in eukaryotic cells. The succinate dehydrogenase complex (Sdhp) plays an important role in respiration as it connects the mitochondrial respiratory chain to the tricarboxylic acid (TCA) cycle where it catalyzes the oxidation of succinate to fumarate. Cellular response to the Sdhp dysfunction (i.e. impaired respiration) thus has important implications not only for biotechnological applications but also for understanding cellular physiology underlying metabolic diseases such as diabetes. We therefore explored the physiological and transcriptional response of Saccharomyces cerevisiae to the deletion of SDH3, that codes for an essential subunit of the Sdhp.ResultsAlthough 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.ConclusionOur 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.
Highlights
Mitochondrial respiration is an important and widely conserved cellular function in eukaryotic cells
We observed a slight increase in succinate production in the mutant strain; yield of 0.0033 g/g-glucose was Inhibition of respiration Shake flask experiments were performed on minimal media to study the effects of three different oxidative phosphorylation inhibitors on the SDH3 mutant
The major inhibitory effects in both strains were observed after treatment with carbonyl cyanide mchlorophenylhydrazone (CCCP) which resulted in reduced specific growth rate and biomass yield in the reference strain, while it completely inhibited growth of sdh3Δ
Summary
Mitochondrial respiration is an important and widely conserved cellular function in eukaryotic cells. The succinate dehydrogenase complex (Sdhp) plays an important role in respiration as it connects the mitochondrial respiratory chain to the tricarboxylic acid (TCA) cycle where it catalyzes the oxidation of succinate to fumarate. 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. The coupling between metabolism and oxidative phosphorylation is reflected in the tight transcriptional regulation of the TCA cycle, for example, as observed in Saccharomyces cerevisiae during the diauxic shift between (page number not for citation purposes)
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