Nejvíce citovaný článek - PubMed ID 25149216
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
During development of yeast colonies, various cell subpopulations form, which differ in their properties and specifically localize within the structure. Three branches of mitochondrial retrograde (RTG) signaling play a role in colony development and differentiation, each of them activating the production of specific markers in different cell types. Here, aiming to identify proteins and processes controlled by the RTG pathway, we analyzed proteomes of individual cell subpopulations from colonies of strains, mutated in genes of the RTG pathway. Resulting data, along with microscopic analyses revealed that the RTG pathway predominantly regulates processes in U cells, long-lived cells with unique properties, which are localized in upper colony regions. Rtg proteins therein activate processes leading to amino acid biosynthesis, including transport of metabolic intermediates between compartments, but also repress expression of mitochondrial ribosome components, thus possibly contributing to reduced mitochondrial translation in U cells. The results reveal the RTG pathway's role in activating metabolic processes, important in U cell adaptation to altered nutritional conditions. They also point to the important role of Rtg regulators in repressing mitochondrial activity in U cells.
- Klíčová slova
- Saccharomyces cerevisiae, colony development and differentiation, mitochondrial retrograde signaling, proteomic analysis, yeast colonies,
- MeSH
- aminokyseliny metabolismus MeSH
- analýza jednotlivých buněk MeSH
- biosyntetické dráhy genetika MeSH
- chromatografie kapalinová MeSH
- intracelulární signální peptidy a proteiny genetika metabolismus MeSH
- mitochondrie genetika metabolismus MeSH
- proteom genetika metabolismus MeSH
- proteomika MeSH
- regulace genové exprese u hub genetika MeSH
- represorové proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae genetika metabolismus MeSH
- signální transdukce genetika MeSH
- tandemová hmotnostní spektrometrie MeSH
- transkripční faktory BHLH-Zip genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aminokyseliny MeSH
- intracelulární signální peptidy a proteiny MeSH
- MKS1 protein, S cerevisiae MeSH Prohlížeč
- proteom MeSH
- represorové proteiny MeSH
- RTG1 protein, S cerevisiae MeSH Prohlížeč
- RTG2 protein, S cerevisiae MeSH Prohlížeč
- RTG3 protein, S cerevisiae MeSH Prohlížeč
- Saccharomyces cerevisiae - proteiny MeSH
- transkripční faktory BHLH-Zip MeSH
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.
- Klíčová slova
- aging, cancer, cell differentiation, mitochondria, retrograde signaling, yeast colonies,
- MeSH
- buněčná diferenciace fyziologie MeSH
- lidé MeSH
- mitochondrie metabolismus MeSH
- signální transdukce fyziologie MeSH
- stárnutí buněk fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- úvodníky MeSH
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