Nejvíce citovaný článek - PubMed ID 22928081
Yeast colonies: a model for studies of aging, environmental adaptation, and longevity
Cell death is a natural part of the development of multicellular organisms and is central to their physiological and pathological states. However, the existence of regulated cell death in unicellular microorganisms, including eukaryotic and prokaryotic microbes, has been a topic of debate. One reason for the continued debate is the lack of obvious benefit from cell death in the context of a single cell. However, unicellularity is relative, as most of these microbes dwell in communities of varying complexities, often with complicated spatial organization. In these spatially organized microbial communities, such as yeast and bacterial colonies and biofilms growing on solid surfaces, cells differentiate into specialized types, and the whole community often behaves like a simple multicellular organism. As these communities develop and age, cell death appears to offer benefits to the community as a whole. This review explores the potential roles of cell death in spatially organized communities of yeasts and draws analogies to similar communities of bacteria. The natural dying processes in microbial cell communities are only partially understood and may result from suicidal death genes, (self-)sabotage (without death effectors), or from non-autonomous mechanisms driven by interactions with other differentiated cells. We focus on processes occurring during the stratification of yeast colonies, the formation of the extracellular matrix in biofilms, and discuss potential roles of cell death in shaping the organization, differentiation, and overall physiology of these microbial structures.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cells must change their properties in order to adapt to a constantly changing environment. Most of the cellular sensing and regulatory mechanisms described so far are based on proteins that serve as sensors, signal transducers, and effectors of signalling pathways, resulting in altered cell physiology. In recent years, however, remarkable examples of the critical role of non-coding RNAs in some of these regulatory pathways have been described in various organisms. In this review, we focus on all classes of non-coding RNAs that play regulatory roles during stress response, starvation, and ageing in different yeast species as well as in structured yeast populations. Such regulation can occur, for example, by modulating the amount and functional state of tRNAs, rRNAs, or snRNAs that are directly involved in the processes of translation and splicing. In addition, long non-coding RNAs and microRNA-like molecules are bona fide regulators of the expression of their target genes. Non-coding RNAs thus represent an additional level of cellular regulation that is gradually being uncovered.
- Klíčová slova
- RNA modifications, epitranscriptome, lncRNA, tRNA, yeast,
- MeSH
- mikro RNA * genetika MeSH
- RNA dlouhá nekódující * genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA * MeSH
- RNA dlouhá nekódující * MeSH
Yeast populations can undergo diversification during their growth and ageing, leading to the formation of different cell-types. Differentiation into two major subpopulations, differing in cell size and density and exhibiting distinct physiological and metabolic properties, was described in planktonic liquid cultures and in populations of colonies growing on semisolid surfaces. Here, we compare stress resistance, metabolism and expression of marker genes in seven differentiated cell subpopulations emerging during cultivation in liquid fermentative or respiratory media and during colony development on the same type of solid media. The results show that the more-dense cell subpopulations are more stress resistant than the less-dense subpopulations under all cultivation conditions tested. On the other hand, respiratory capacity, enzymatic activities and marker gene expression differed more between subpopulations. These characteristics are more influenced by the lifestyle of the population (colony vs. planktonic cultivation) and the medium composition. Only in the population growing in liquid respiratory medium, two subpopulations do not form as in the other conditions tested, but all cells exhibit a range of characteristics of the more-dense subpopulations. This suggests that signals for cell differentiation may be triggered by prior metabolic reprogramming or by an unknown signal from the structured environment in the colony.
We present the spatiotemporal metabolic differentiation of yeast cell subpopulations from upper, lower, and margin regions of colonies of different ages, based on comprehensive transcriptomic analysis. Furthermore, the analysis was extended to include smaller cell subpopulations identified previously by microscopy within fully differentiated U and L cells of aged colonies. New data from RNA-seq provides both spatial and temporal information on cell metabolic reprogramming during colony ageing and shows that cells at marginal positions are similar to upper cells, but both these cell types are metabolically distinct from cells localized to lower colony regions. As colonies age, dramatic metabolic reprogramming occurs in cells of upper regions, while changes in margin and lower cells are less prominent. Interestingly, whereas clear expression differences were identified between two L cell subpopulations, U cells (which adopt metabolic profiles, similar to those of tumor cells) form a more homogeneous cell population. The data identified crucial metabolic reprogramming events that arise de novo during colony ageing and are linked to U and L cell colony differentiation and support a role for mitochondria in this differentiation process.
Mitochondrial retrograde signaling mediates communication from altered mitochondria to the nucleus and is involved in many normal and pathophysiological changes, including cell metabolic reprogramming linked to cancer development and progression in mammals. The major mitochondrial retrograde pathway described in yeast includes three activators, Rtg1p, Rtg2p and Rtg3p, and repressors, Mks1p and Bmh1p/Bmh2p. Using differentiated yeast colonies, we show that Mks1p-Rtg pathway regulation is complex and includes three branches that divergently regulate the properties and fate of three specifically localized cell subpopulations via signals from differently altered mitochondria. The newly identified RTG pathway-regulated genes ATO1/ATO2 are expressed in colonial upper (U) cells, the cells with active TORC1 that metabolically resemble tumor cells, while CIT2 is a typical target induced in one subpopulation of starving lower (L) cells. The viability of the second L cell subpopulation is strictly dependent on RTG signaling. Additional co-activators of Rtg1p-Rtg3p specific to particular gene targets of each branch are required to regulate cell differentiation.
- Klíčová slova
- ageing and longevity, development and differentiation, mitochondrial retrograde signaling,
- MeSH
- buněčná diferenciace fyziologie MeSH
- geny hub fyziologie MeSH
- mitochondrie metabolismus MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae fyziologie MeSH
- signální transdukce fyziologie MeSH
- viabilita buněk fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Saccharomyces cerevisiae - proteiny MeSH
Colonies of Saccharomyces cerevisiae laboratory strains pass through specific developmental phases when growing on solid respiratory medium. During entry into the so-called alkali phase, in which ammonia signaling is initiated, 2 prominent cell types are formed within the colonies: U cells in upper colony regions, which have a longevity phenotype and activate the expression of a large number of metabolic genes, and L cells in lower regions, which die more quickly and exhibit a starvation phenotype. Here, we performed a detailed analysis of the activities of enzymes of central carbon metabolism in lysates of both cell types and determined several fermentation end products, showing that previously reported expression differences are reflected in the different enzymatic capabilities of each cell type. Hence, U cells, despite being grown on respiratory medium, behave as fermenting cells, whereas L cells rely on respiratory metabolism and possess active gluconeogenesis. Using a spectrum of different inhibitors, we showed that glycolysis is essential for the formation, and particularly, the survival of U cells. We also showed that β-1,3-glucans that are released from the cell walls of L cells are the most likely source of carbohydrates for U cells.
- Klíčová slova
- enzymatic assays, fermentation, metabolic differentiation, respiration, yeast colonies,
- MeSH
- beta-glukany metabolismus MeSH
- buněčná stěna metabolismus MeSH
- časové faktory MeSH
- fenotyp MeSH
- fermentace * účinky léků MeSH
- genotyp MeSH
- glykolýza * účinky léků MeSH
- inhibitory enzymů farmakologie MeSH
- kultivační média chemie metabolismus MeSH
- mikrobiální viabilita MeSH
- mikrobiologické techniky metody MeSH
- počet mikrobiálních kolonií MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae účinky léků enzymologie genetika růst a vývoj MeSH
- sériové pasážování MeSH
- substrátová specifita MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-glukany MeSH
- inhibitory enzymů MeSH
- kultivační média MeSH
- Saccharomyces cerevisiae - proteiny MeSH
