Cyclic changes in metabolic state during the life of a yeast cell

Abstract

Budding yeast undergo robust oscillations in oxygen consumption during continuous growth in a nutrient-limited environment. Using liquid chromatography-mass spectrometry and comprehensive 2D gas chromatography-mass spectrometry-based metabolite profiling methods, we have determined that the intracellular concentrations of many metabolites change periodically as a function of these metabolic cycles. These results reveal the logic of cellular metabolism during different phases of the life of a yeast cell. They may further indicate that oscillation in the abundance of key metabolites might help control the temporal regulation of cellular processes and the establishment of a cycle. Such oscillations in metabolic state might occur during the course of other biological cycles.gas chromatography-mass spectrometry ͉ liquid chromatography-mass spectrometry ͉ metabolic cycle ͉ metabolite profiling C ircadian rhythms are driven by biological clocks found in virtually all kingdoms of life (1, 2). Genome-wide expression studies in plants, flies, and mice have shown that many genes are expressed periodically as a function of the circadian cycle (3-6). It is now predictable from studies of oscillating gene expression that the circadian regulatory apparatus should differentially control metabolic state as a function of the circadian cycle (7,8). By contrast, direct and comprehensive measurements of changes in sentinel metabolites have not been performed as a function of the circadian cycle or of biological cycles of other temporal dimensions.The budding yeast Saccharomyces cerevisiae exhibits various modes of oscillatory behavior during continuous growth (9-12). We recently established a continuous culture system that reveals an Ϸ4-to 5-h yeast metabolic cycle (YMC) in which over half of the genome is periodically expressed as a function of robust recurring oscillations in oxygen consumption (12). Expression profiling studies have led to the prediction that a variety of cellular and metabolic processes are temporally orchestrated around three major phases of the YMC [oxidative (Ox), reductive/building (RB), and reductive/ charging (RC)] (12). Cells undergoing the YMC are furthermore synchronized with respect to the cell cycle, because the YMC strictly gates cell division to the RB phase when respiration decreases significantly (12).A prediction of temporal compartmentalization is that the concentrations of critical metabolites might exhibit periodic fluctuation and, in turn, play a reciprocal role in regulating the YMC (8). To determine whether cyclic changes in metabolic state might occur during the YMC, we used both liquid chromatography (LC)/ tandem mass spectrometry (LC-MS/MS) and comprehensive 2D gas chromatography (GC)/time-of-f light mass spectrometry (GCϫGC-TOFMS) to monitor the intracellular concentrations of Ϸ150 common metabolites at regularly spaced intervals throughout the YMC. The combined use of LC-MS-and GC-MS-based methods provides a means to evaluate the consistency of results for metabolites detected by both ...

Autoacetylation of the Histone Acetyltransferase Rtt109

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“…3B and Dataset S1). Another striking function conserved between the two systems includes the pentosephosphate pathway (23). This pathway plays a major role in the production of NADPH (a reduced form of NADP+), a key metabolite that provides the cell with reductive power, and which is involved in the production of intermediates for many biosynthetic reactions.…”

Acetyl-CoA induces transcription of the key G1 cyclin CLN3 to promote entry into the cell division cycle in Saccharomyces cerevisiae

“…In the YMC, a highly synchronized cell population undergoes robust oscillations in oxygen consumption and metabolism that are coupled to the cell cycle, during continuous glucose-limited growth (37,38). Microarray analysis of gene expression during the YMC has revealed that over half of all yeast genes are periodically expressed according to a specified logic.…”