Vol. 02, 2015
A bacterial volatile signal for biofilm formation
Yun Chen2, Kevin Gozzi1, and Yunrong Chai1
Bacteria constantly monitor the environment they reside in and respond to potential changes in the environment through a variety of signal sensing and transduction mechanisms in a timely fashion. In their recent study (Chen, et al. mBio (2015), 6: e00392-15), the authors demonstrated that the soil bacterium Bacillus subtilis uses acetic acid as a volatile signal to coordinate the timing of biofilm formation within physically separated cells in the community. They also showed that the bacterium possesses an intertwined gene network to produce, secrete, sense, and respond to acetic acid, in stimulating biofilm formation.
Elongation factor-P at the crossroads of the host-endosymbiont interface
Andrei Rajkovic1, Anne Witzky2, William Navarre3, Andrew J. Darwin4 and Michael Ibba5
Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. Here, the authors highlight the recent discoveries made regarding EPMSs, with a focus on how these incomplete modification pathways shape or have been shaped by the endosymbiont-host relationship.
The great escape: Pseudomonas breaks out of the lung
Angelica Zhang1, Stephanie M. Rangel1, and Alan R. Hauser1,2
The Gram-negative bacterium Pseudomonas aeruginosa is a major cause of hospital-acquired infections and the focus of much attention due to its resistance to many conventional antibiotics. This article discusses the potential mechanisms by which these processes occur as well as the novel techniques used to study ExoS function in vivo.
DNA damage checkpoint adaptation genes are required for division of cells harbouring eroded telomeres
Sofiane Y. Mersaoui, Serge Gravel, Victor Karpov, and Raymund J. Wellinger
In budding yeast, telomerase and the Cdc13p protein are two key players acting to ensure telomere stability. This article shows that while the capping process can be flexible, it takes a very specific genetic setup to allow a change from canonical capping to alternative capping.
The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway
Chunyan Jin#, Stephen K. Kim, Stephen D. Willis and Katrina F. Cooper
Oxidative stress stimulates the Rho1 GTPase, which in turn induces the cell wall integrity (CWI) MAP kinase cascade. CWI activation promotes stress-responsive gene expression through activation of transcription factors (Rlm1, SBF) and nuclear release and subsequent destruction of the repressor cyclin C. This study reports that, in response to high hydrogen peroxide exposure, or in the presence of constitutively active Rho1, cyclin C still translocates to the cytoplasm and is degraded in cells lacking Bck1, the MAPKKK of the CWI pathway.
Feelin’ it: Differential oxidative stress sensing mediated by Cyclin C
W. Scott Moye-Rowley
Microbial cells that live exposed directly to their environmental milieu are faced with the challenge of adapting to the dynamic stress conditions that will inevitably be encountered. These stress conditions may vary over wide ranges and the most efficient responses would be tuned to produce a proportional buffering change. A mild stress would most efficiently be dealt with by a mild metabolic reprogramming that would prevent serious damage. A more severe environmental challenge would demand a more dramatic cellular compensatory response.
Formyl-methionine as a degradation signal at the N-termini of bacterial proteins
Konstantin I. Piatkov1,3,#, Tri T. M. Vu1,#, Cheol-Sang Hwang2 and Alexander Varshavsky1
Varshavsky and colleagues solve a long-standing mystery in proteolysis! In bacteria, all nascent proteins bear the pretranslationally formed N-terminal formyl-methionine (fMet) residue. The fMet residue is cotranslationally deformylated by a ribosome-associated deformylase. The formylation of N-terminal Met in bacterial proteins is not strictly essential for either translation or cell viability. Moreover, protein synthesis by the cytosolic ribosomes of eukaryotes does not involve the formylation of N-terminal Met. What, then, is the main biological function of this metabolically costly, transient, and not strictly essential modification of N‑terminal Met, and why has Met formylation not been eliminated during bacterial evolution? One possibility is that the similarity of the formyl and acetyl groups, their identical locations in...
Peering into the ‘black box’ of pathogen recognition by cellular autophagy systems
Shu-chin Lai# and Rodney J Devenish
Autophagy is an intracellular process that plays an important role in protecting eukaryotic cells and maintaining intracellular homeostasis. This review summarises the available evidence regarding the specific recognition of invading pathogens by which they are targeted into host autophagy pathways.
Per aspera ad astra: When harmful chromosomal translocations become a plus value in genetic evolution. Lessons from Saccharomyces cerevisiae
Valentina Tosato and Carlo V. Bruschi
This review will focus on chromosomal translocations (either spontaneous or induced) in budding yeast. Indeed, very few organisms tolerate so well aneuploidy like Saccharomyces, allowing in depth studies on chromosomal numerical aberrations. The phenomenon of post-translocational adaptation (PTA) is discussed, providing some new unpublished data and proposing the hypothesis that translocations may drive evolution through adaptive genetic selection.
Groupthink: chromosomal clustering during transcriptional memory
Kevin A. Morano
In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.
Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration
Amit Shrestha1, 2 and Lynn A. Megeney1, 2, 3
Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.
INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering
Donna Garvey Brickner, Robert Coukos and Jason H. Brickner
Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
Michael E. Bond1, Rachel Brown1, Charalampos Rallis3,4, Jürg Bähler3,4 and Sara E. Mole1,2,3
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.
Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi
Alberto Elías-Villalobos1,2, Dominique Helmlinger2 and José I. Ibeas1
Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Elías-Villalobos et al. propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.
Cytokinins beyond plants: synthesis by Mycobacterium tuberculosis
Marie I. Samanovic and K. Heran Darwin
This microreview discusses "Proteasomal Control of Cytokinin Synthesis Protects Mycobacterium tuberculosis against Nitric Oxide" by Samanovic et al. (2015), Mol Cell.
Yeast as a model system to study metabolic impact of selenium compounds
Enrique Herrero1,* and Ralf Erik Wellinger2
Inorganic Se forms such as selenate or selenite (the two more abundant forms in nature) can be toxic in Saccharomyces cerevisiae cells, which constitute an adequate model to study such toxicity at the molecular level and the functions participating in protection against Se compounds. In this article, the authors propose that yeast may be used to improve our knowledge on the impact of Se on metal homeostasis, the identification of Se-targets at the DNA and protein levels, and to gain more insights into the mechanism of Se-mediated apoptosis.
Understanding structure, function, and mutations in the mitochondrial ATP synthase
Ting Xu1, Vijayakanth Pagadala2, David M. Mueller1
This review summarizes the current understanding of the subunit composition of the ATP synthase and the role of the subunits followed by a discussion on known mutations and their effect on the activity of the ATP synthase. The concludes with a summary of mutations in genes encoding subunits of the ATP synthase that are known to be responsible for human disease, and a brief discussion on SNPs.
Modeling non-hereditary mechanisms of Alzheimer disease during apoptosis in yeast
Ralf J. Braun1,#, Cornelia Sommer2,3,#, Christine Leibiger1,#, Romina J.G. Gentier4,#, Verónica I. Dumit5, Katrin Paduch1, Tobias Eisenberg2, Lukas Habernig2, Gert Trausinger6, Christoph Magnes6, Thomas Pieber6,7, Frank Sinner6,7, Jörn Dengjel5, Fred W. van Leeuwen4, Guido Kroemer8-11, and Frank Madeo2,3
Impaired protein degradation and mitochondrial dysfunction are believed to contribute to neurodegenerative disorders, including Alzheimer disease (AD). This microreview comments on the article "Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin" by Braun et al. (2015), Cell Rep.
Translate to divide: сontrol of the cell cycle by protein synthesis
Michael Polymenis1 and Rodolfo Aramayo2
Protein synthesis underpins much of cell growth and, consequently, cell multiplication. Understanding how proliferating cells commit and progress into the cell cycle requires knowing not only which proteins need to be synthesized, but also what determines their rate of synthesis during cell division. Experiments with proliferating populations of microbial strains, animal or plant cell lines, have rigorous expectations. Under the same culture conditions, cells ought to have the same properties and composition in every single experiment. The basic “metrics” of proliferating cells remain constant, even after many rounds of cell division. These metrics include cellular mass and volume, and macromolecular composition. The constancy of such parameters reflects the fundamental ability of cells to coordinate their growth with their division. Balancing cell growth with cell division determines the overall rates of cell proliferation...
New roles for autophagy and spermidine in T cells
D. J. Puleston and A. K. Simon
This microreview discusses the article "Autophagy is a critical regulator of memory CD8+ T cell formation" by Puleston et al. (2014), eLife.
Characterization of the Maf family of polymorphic toxins in pathogenic Neisseria species
Anne Jamet1,2,3,4,5, Xavier Nassif2,3,4,5
In addition to harmless commensal species, Neisseria genus encompasses two pathogenic species, N. meningitidis (the meningococcus) and N. gonorrhoeae (the gonococcus), which are responsible for meningitis and genital tract infections, respectively. This microreview comments on the article "A new family of secreted toxins in pathogenic Neisseria species" by Jamet et al. (2015), PLoS Pathog.
Live fast, die soon: cell cycle progression and lifespan in yeast cells
Javier Jiménez, Samuel Bru, Mariana PC Ribeiro and Josep Clotet
Our understanding of lifespan has benefited enormously from the study of a simple model, the yeast Saccharomyces cerevisiae. Although a unicellular organism, yeasts undergo many of the processes directly related with aging that to some extent are conserved in mammalian cells. Nutrient-limiting conditions have been involved in lifespan extension, especially in the case of caloric restriction, which also has a direct impact on cell cycle progression. In fact, other environmental stresses (osmotic, oxidative) that interfere with normal cell cycle progression also influence the lifespan of cells, indicating a relationship between lifespan and cell cycle control. In the present review we compile and discuss new findings related to how cell cycle progression is regulated by other nutrients. We centred this review on the analysis of phosphate, also give some attention to nitrogen, and the impact of these nutrients on lifespan...
Yeast as a tool for studying proteins of the Bcl-2 family
Peter Polčic, Petra Jaká and Marek Mentel
This review focuses on using yeast expressing mammalian proteins of the Bcl-2 family as a tool to investigate mechanisms, by which these proteins permeabilize mitochondrial membranes, mechanisms, by which pro- and antiapoptotic members of this family interact, and involvement of other cellular components in the regulation of programmed cell death by Bcl-2 family proteins.
Groupthink: chromosomal clustering during transcriptional memory
Kevin A. Morano
In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.
Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration
Amit Shrestha1, 2 and Lynn A. Megeney1, 2, 3
Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.
Starting with a degron: N-terminal formyl-methionine of nascent bacterial proteins contributes to their proteolytic control
R. Jürgen Dohmen
In this article, the author comments on the study "Formyl-methionine as a degradation signal at the N-termini of bacterial proteins." by Piatkov et al. (Microbial Cell, 2015), discussing a novel N-terminal degradation signal (N-degron) that targets nascent proteins for degradation in Escherichia coli by a new branch of the bacterial N-end rule pathway, termed the fMet/N-end rule pathway
Elongation factor-P at the crossroads of the host-endosymbiont interface
Andrei Rajkovic1, Anne Witzky2, William Navarre3, Andrew J. Darwin4 and Michael Ibba5
Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. Here, the authors highlight the recent discoveries made regarding EPMSs, with a focus on how these incomplete modification pathways shape or have been shaped by the endosymbiont-host relationship.
Feelin’ it: Differential oxidative stress sensing mediated by Cyclin C
W. Scott Moye-Rowley
Microbial cells that live exposed directly to their environmental milieu are faced with the challenge of adapting to the dynamic stress conditions that will inevitably be encountered. These stress conditions may vary over wide ranges and the most efficient responses would be tuned to produce a proportional buffering change. A mild stress would most efficiently be dealt with by a mild metabolic reprogramming that would prevent serious damage. A more severe environmental challenge would demand a more dramatic cellular compensatory response.
Subverting lysosomal function in Trypanosoma brucei
Sam Alsford
This article discusses Koh et al. (2015) "The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei (Microbial Cell 2(8): 288-298).
Toxoplasma control of host apoptosis: the art of not biting too hard the hand that feeds you
Sébastien Besteiro
Toxoplasma gondii is an obligate intracellular parasite that is able to infect a multitude of different vertebrate hosts and can survive in virtually any nucleated cell. Here, the authors discuss the article "Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly" by Graumann et al. (2015, Microbial Cell).
A safety catch for ornithine decarboxylase degradation
Christof Taxis
Feedback inhibition is a common mechanism to adjust the activity of an enzyme in accordance with the abundance of a product. This article comments on the study "Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome" by Beenukumar et al. (2015), Microbial Cell.
Fancy a gene? A surprisingly complex evolutionary history of peroxiredoxins.
Alena Zíková1,2, Miroslav Oborník1,2,3 and Julius Lukeš1,2,4
In this comment, the authors discuss the article "Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites" (Djuika et al., Microbial Cell 2015).
Groupthink: chromosomal clustering during transcriptional memory
November 26, 2015
In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.
Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration
November 26, 2015
Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.
INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering
November 13, 2015
Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
November 11, 2015
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.
Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi
November 4, 2015
Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Elías-Villalobos et al. propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.
Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae
October 22, 2015
Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of...
Electron microscopy for ultrastructural analysis and protein localization in Saccharomyces cerevisiae
October 12, 2015
The yeast Saccharomyces cerevisiae is a key model system for studying of a multitude of cellular processes because of its amenability to genetics, molecular biology and biochemical procedures. The goal of this review is to guide researchers that want to investigate a particular process at the ultrastructural level in yeast by aiding in the selection of the most appropriate approach to visualize a specific structure or subcellular compartment.
Starting with a degron: N-terminal formyl-methionine of nascent bacterial proteins contributes to their proteolytic control
October 4, 2015
In this article, the author comments on the study "Formyl-methionine as a degradation signal at the N-termini of bacterial proteins." by Piatkov et al. (Microbial Cell, 2015), discussing a novel N-terminal degradation signal (N-degron) that targets nascent proteins for degradation in Escherichia coli by a new branch of the bacterial N-end rule pathway, termed the fMet/N-end rule pathway
A bacterial volatile signal for biofilm formation
September 23, 2015
Bacteria constantly monitor the environment they reside in and respond to potential changes in the environment through a variety of signal sensing and transduction mechanisms in a timely fashion. In their recent study (Chen, et al. mBio (2015), 6: e00392-15), the authors demonstrated that the soil bacterium Bacillus subtilis uses acetic acid as a volatile signal to coordinate the timing of biofilm formation within physically separated cells in the community. They also showed that the bacterium possesses an intertwined gene network to produce, secrete, sense, and respond to acetic acid, in stimulating biofilm formation.