Vol. 02, 2015
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.
Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae
Markus M.M. Bisschops1,3,#, Tim Vos1,#, Rubén Martínez-Moreno2,4, Pilar de la Torre Cortés1, Jack T. Pronk1, Pascale Daran-Lapujade1
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
Andri Frankl, Muriel Mari and Fulvio Reggiori
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
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
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.
From the baker to the bedside: yeast models of Parkinson’s disease
Regina Menezes1,2, Sandra Tenreiro3,5, Diana Macedo2, Cláudia N. Santos1,2, Tiago Fleming Outeiro4,5,6
The baker’s yeast Saccharomyces cerevisiae has been extensively explored for our understanding of fundamental cell biology processes highly conserved in the eukaryotic kingdom. This review provides a brief historical perspective on the emergence of yeast as an experimental model and on how the field evolved to exploit the potential of the model for tackling the intricacies of various human diseases. In particular, the authors focus on existing yeast models of the molecular underpinnings of Parkinson’s disease (PD), focusing primarily on the central role of protein quality control systems.
Why are essential genes essential? – The essentiality of Saccharomyces genes
Zhaojie Zhang and Qun Ren
Essential genes are defined as required for the survival of an organism or a cell. This article reviews and analyzes the levels of essentiality of the Saccharomyces cerevisiae genes and groups the genes into four categories: (1) Conditional essential: essential only under certain circumstances or growth conditions; (2) Essential: required for survival under optimal growth conditions; (3) Redundant essential: synthetic lethal due to redundant pathways or gene duplication; and (4) Absolute essential: the minimal genes required for maintaining a cellular life under a stress-free environment. The essential and non-essential functions of the essential genes are further analyzed.
Evolutionary rewiring of bacterial regulatory networks
Tiffany B. Taylor1,*, Geraldine Mulley1, Liam J. McGuffin1, Louise J. Johnson1, Michael A. Brockhurst2, Tanya Arseneault1,3, Mark W. Silby4 and Robert W. Jackson1,5
Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks – homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. This article discusses Taylor, et al. Science (2015), 347(6225), reporting mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but which come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.
Wanted Plasmodium falciparum, dead or alive
Fatimata Sow1, Mary Nyonda1, Anne-Lise Bienvenu1, 2, Stephane Picot1, 2
In this article, mechanisms of cell death in unicellular parasites are discussed, focussing on “programmed cell death” in Plasmodium.
Yeast as a tool to explore cathepsin D function
H. Pereira1, C.S.F. Oliveira1,2, L. Castro1, A. Preto1, S. R. Chaves1,#, M. Côrte-Real1,#
Cathepsin D has garnered increased attention in recent years, mainly since it has been associated with several human pathologies. This review summarizes how cathepsin D can have both anti- and pro-survival functions depending on its proteolytic activity, cellular context and stress stimulus.
Coordinate responses to alkaline pH stress in budding yeast
Albert Serra-Cardona, David Canadell and Joaquín Ariño
This review summarizes the modulation of a substantial number of signaling pathways whose participate in the alkaline response in yeast. These regulatory inputs involve not only the conserved Rim101/PacC pathway, but also the calcium-activated phosphatase calcineurin, the Wsc1-Pkc1-Slt2 MAP kinase, the Snf1 and PKA kinases and oxidative stress-response pathways.
Handcuffs for bacteria – NDP52 orchestrates xenophagy of intracellular Salmonella
Pauline Verlhac1,2,3,4,5, Christophe Viret1,2,3,4,5 and Mathias Faure1,2,3,4,5
This microreview discusses the article "Autophagy Receptor NDP52 Regulates Pathogen-Containing Autophagosome Maturation" by Verlhac et al. (2015), Cell Host Microbe.
Understanding grapevine-microbiome interactions: implications for viticulture industry
Iratxe Zarraonaindia1,2 and Jack A. Gilbert3,4,5,6
This microreview discusses the article "The soil microbiome influences grapevine-associated microbiota" by Zarraonaindia et al. (2015), MBio, which reports that the grapevine-associated microbiota depends on the soil microbiome.
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).
Mitochondrial type II NAD(P)H dehydrogenases in fungal cell death
March 2, 2015
During aerobic respiration, cells produce energy through oxidative phosphorylation, which includes a specialized group of multi-subunit complexes in the inner mitochondrial membrane known as the electron transport chain. However, this canonical pathway is branched into single polypeptide alternative routes in some fungi, plants, protists and bacteria. They confer metabolic plasticity, allowing cells to adapt to different environmental conditions and stresses...
Fancy a gene? A surprisingly complex evolutionary history of peroxiredoxins.
January 28, 2015
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).
Quorum protection, growth and survival
January 23, 2015
For the growth of a cell culture, one inoculates not with one cell but with a quorum of cells. This most often a requirement, not just a convenience, and most of us take this for granted without question. Here this observation is re-examined to understand why a quorum may be required to grow cells. The importance of quorums may be widespread in the aspects of microbiology they affect. It is very likely that quorums are connected with and have a large impact on the determination of Minimal Inhibitory Concentrations. It is also possible that low cell density may adversely affect cell survival, however, this is an area where even less is known. The need for a quorum might affect other aspects of microbial cell culture, cell isolation and cell preservation. Effects also extend to mammalian cell culture. Here I seek to review studies that have been documented and speculate on how the information might be utilized in the future.
EzrA: a spectrin-like scaffold in the bacterial cell division machinery
January 15, 2015
Much progress has been made in identifying the components of the divisome, the assembly of proteins that undertakes the vital process of cell division in bacteria. However, how the highly interdependent processes on either side of the membrane are coordinated during division is a major unresolved question. This comment discusses the article "Structure and function of a spectrin-like regulator of bacterial cytokinesis" by Cleverley et al. (2014), Nat Commun.
Microbial hara-kiri: Exploiting lysosomal cell death in malaria parasites
January 12, 2015
The antimalarial drug chloroquine (CQ) has been sidelined in the fight against falciparum malaria due to wide-spread CQ resistance. This comment discusses the article "Validation of a chloroquine-induced cell death mechanism for clinical use against malaria" by Ch'ng et al. (2014), Cell Death Dis.
Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites
January 4, 2015
Horizontal gene transfer has emerged as a crucial driving force for the evolution of eukaryotes. This also includes Plasmodium falciparum and related economically and clinically relevant apicomplexan parasites, whose rather small genomes have been shaped not only by natural selection in different host populations but also by horizontal gene transfer following endosymbiosis. However, there is rather little reliable data on horizontal gene transfer between animal hosts or bacteria and apicomplexan parasites. Here we show that apicomplexan homologues of peroxiredoxin 5 (Prx5) have a prokaryotic ancestry and therefore represent a special subclass of Prx5 isoforms in eukaryotes. Using two different immunobiochemical approaches, we found that...
The emerging role of complex modifications of tRNALysUUU in signaling pathways
January 4, 2015
This comment discusses the article "Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling" by Scheidt et al (Microbial Cell, 2014).
Two distinct and competitive pathways confer the cellcidal actions of artemisinins
January 1, 2015
The biological actions of artemisinin (ART), an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. This article concludes that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.
A pseudokinase couples signaling pathways to enable asymmetric cell division in a bacterium
December 30, 2014
In this article, the authors comment on the study "Cell fate regulation governed by a repurposed bacterial histidine kinase" by Childers et al., PLoS Biol. 2014 Oct 28;12(10):e1001979.