A conserved cell growth cycle can account for the environmental stress responses of divergent eukaryotes

Departments of Physics and Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Molecular biology of the cell (Impact Factor: 4.47). 03/2012; 23(10):1986-97. DOI: 10.1091/mbc.E11-11-0961
Source: PubMed


The respiratory metabolic cycle in budding yeast (Saccharomyces cerevisiae) consists of two phases that are most simply defined phenomenologically: low oxygen consumption (LOC) and high oxygen consumption (HOC). Each phase is associated with the periodic expression of thousands of genes, producing oscillating patterns of gene expression found in synchronized cultures and in single cells of slowly growing unsynchronized cultures. Systematic variation in the durations of the HOC and LOC phases can account quantitatively for well-studied transcriptional responses to growth rate differences. Here we show that a similar mechanism-transitions from the HOC phase to the LOC phase-can account for much of the common environmental stress response (ESR) and for the cross-protection by a preliminary heat stress (or slow growth rate) to subsequent lethal heat stress. Similar to the budding yeast metabolic cycle, we suggest that a metabolic cycle, coupled in a similar way to the ESR, in the distantly related fission yeast, Schizosaccharomyces pombe, and in humans can explain gene expression and respiratory patterns observed in these eukaryotes. Although metabolic cycling is associated with the G0/G1 phase of the cell division cycle of slowly growing budding yeast, transcriptional cycling was detected in the G2 phase of the division cycle in fission yeast, consistent with the idea that respiratory metabolic cycling occurs during the phases of the cell division cycle associated with mass accumulation in these divergent eukaryotes.

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Available from: Nikolai Slavov
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    • "In C. albicans , the existence of ESR was debated [21] but a relatively small group of ESR genes (62 genes) was identified at last under the control of Hog1 mitogen activated protein kinase (MAPK) [17, 22]. Importantly, the way of counting ESR genes has not been standardized yet and seems to be dependent on the dose of stress [17, 21, 22] and the rate of growth [23, 24]. Furthermore, global transcriptional responses to oxidative stress and their regulations were dependent on the type and dose of stress in S. pombe [25] , and also on the presence or absence of another bZIP-type transcription factor Pcr1, which form heterodimers with Atf1262728. "
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    • "Slavov and Botstein observed growth rate signals to be a function of the abundance of essential nutrients, which (in turn) regulate fermentation/respiration , the growth rate response, and the cell division cycle [13] [14]. The coupling between oxygen availability, transcriptional changes leading to growth rate differences and the environmental stress response was discussed previously [15]. Airoldi et al. [16] computationally predicted the strong up-regulation of growth as a response to the absence of appropriate nutrients. "
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    ABSTRACT: There is an increasing use of systems biology approaches in both "red" and "white" biotechnology in order to enable medical, medicinal, and industrial applications. The intricate links between genotype and phenotype may be explained through the use of the tools developed in systems biology, synthetic biology, and evolutionary engineering. Biomedical and biotechnological research are among the fields that could benefit most from the elucidation of this complex relationship. Researchers have studied fitness extensively to explain the phenotypic impacts of genetic variations. This elaborate network of dependencies and relationships so revealed are further complicated by the influence of environmental effects that present major challenges to our achieving an understanding of the cellular mechanisms leading to healthy or diseased phenotypes or optimized production yields. An improved comprehension of complex genotype-phenotype interactions and their accurate prediction should enable us to more effectively engineer yeast as a cell factory and to use it as a living model of human or pathogen cells in intelligent screens for new drugs. This review presents different methods and approaches undertaken toward improving our understanding and prediction of the growth phenotype of the yeast Saccharomyces cerevisiae as both a model and a production organism.
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    • "It would be no surprise if changes in ribosome biogenesis were accompanied by changes in other processes such as energy generation and protein turnover. Consistent with this idea, genome-wide studies point to large, antagonistic human gene networks whose expression changes as proliferation gives way to differentiation [47], and indicate that expression of a significant fraction of eukaryote genomes may be regulated by growth rate [48]. These studies have been based on changes during aging or in nutrient availability, however, and it remains to be seen how regulation occurs during developmental patterning, when cellular growth rate can even differ within the same tissue at the same time, as seems to be the case in the eye imaginal disc. "
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