Vol. 02, 2015

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 Jamet^1,2,3,4,5, Xavier Nassif^2,3,4,5

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.

Mitochondrial type II NAD(P)H dehydrogenases in fungal cell death

Pedro Gonçalves^1,2,4, Arnaldo Videira^1,2,3

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...

Arabidopsis Bax Inhibitor-1 inhibits cell death induced by pokeweed antiviral protein in Saccharomyces cerevisiae

Birsen Cakir^1,2 and Nilgun E. Tumer¹

Apoptosis is an active form of programmed cell death (PCD) that plays critical roles in the development, differentiation and resistance to pathogens in multicellular organisms. Both full length and C-terminal deleted AtBI-1 were capable of binding to PAP. These findings indicate that PAP induces cell death in yeast and AtBI-1 inhibits cell death induced by PAP without affecting ribosome depurination and translation inhibition.

Fancy a gene? A surprisingly complex evolutionary history of peroxiredoxins.

Alena Zíková^1,2, Miroslav Oborník^1,2,3 and Julius Lukeš^1,2,4

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).

Quorum protection, growth and survival

Ian G . Macreadie

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.

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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 Shrestha^{1, 2} and Lynn A. Megeney^{1, 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 Rallis^3,4, Jürg Bähler^3,4 and Sara E. Mole^1,2,3

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-Villalobos^1,2, 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.

Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin

Fazal Shirazi¹, Russel E. Lewis^1,2, Dimitrios P. Kontoyiannis¹

Shirazi et al. studied the effects of the cell wall inhibitor micafungin (MICA) on apoptosis in both MICA-susceptible (MICA-S) and MICA–non-susceptible (MICA-NS) Candida parapsilosis.

Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi

Alberto Elías-Villalobos^1,2, Dominique Helmlinger² and José I. Ibeas¹

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.

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.

The great escape: Pseudomonas breaks out of the lung

Angelica Zhang¹, Stephanie M. Rangel¹, and Alan R. Hauser^1,2

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.

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.

Intracellular phase for an extracellular bacterial pathogen: MgtC shows the way

Audrey Bernut^1,#, Claudine Belon¹, Chantal Soscia², Sophie Bleves², Anne-Béatrice Blanc-Potard¹

This article discusses the article "A macrophage subversion factor is shared by intracellular and extracellular pathogens" by Belon et al. (PLoS Pathogens 11(6): e1004969, 2015).

The role of transcriptional ‘futile cycles’ in autophagy and microbial pathogenesis

Guowu Hu¹, Travis McQuiston¹, Amélie Bernard², Yoon-Dong Park¹, Jin Qiu¹, Ali Vural³, Nannan Zhang¹, Scott R. Waterman¹, Nathan H. Blewett⁴, Timothy G. Myers⁵, John H. Kehrl³, Gulbu Uzel¹, Daniel J. Klionsky² and Peter R. Williamson¹

Eukaryotic cells utilize macroautophagy (hereafter autophagy) to recycle cellular materials during nutrient stress. Target of rapamycin (Tor) is a central regulator of this process, acting by post-translational mechanisms, phosphorylating preformed autophagy-related (Atg) proteins to repress autophagy during log-phase growth. A role for this regulatory process in fungal virulence was further demonstrated by showing that overexpression of the Dcp2-associated mRNA-binding protein Vad1 in the AIDS-associated pathogen Cryptococcus neoformans results in constitutive repression of autophagy even under starvation conditions as well as attenuated virulence in a mouse model. In summary, Tor-dependent post-transcriptional regulation of autophagy plays a key role in the facilitation of microbial pathogenesis.

The many facets of homologous recombination at telomeres

Clémence Claussin and Michael Chang

The ends of linear chromosomes are capped by nucleoprotein structures called telomeres. A dysfunctional telomere may resemble a DNA double-strand break (DSB), which is a severe form of DNA damage. The presence of one DSB is sufficient to drive cell cycle arrest and cell death. Therefore cells have evolved mechanisms to repair DSBs such as homologous recombination (HR). HR-mediated repair of telomeres can lead to genome instability, a hallmark of cancer cells, which is why such repair is normally inhibited. However, some HR-mediated processes are required for proper telomere function. The need for some recombination activities at telomeres but not others necessitates careful and complex regulation, defects in which can lead to catastrophic consequences. Furthermore, some cell types can maintain telomeres via telomerase-independent, recombination-mediated mechanisms. In humans, these mechanisms...

Quorum protection, growth and survival

Ian G . Macreadie

The emerging role of complex modifications of tRNA^Lys_UUU in signaling pathways

Patrick C. Thiaville^1,2,3,4 and Valérie de Crécy-Lagard^2,4

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).

Exogenous folates stimulate growth and budding of Candida glabrata

May 1, 2015

Folate, vitamin B9, is well recognized as being essential for cell growth. The utilization of folate is common to all cells, but the source of it may be quite different. This article reports a novel response of yeast to folates that may increase the utility of yeast as a model to study folate transport and signaling.

Yeast as a model system to study metabolic impact of selenium compounds

April 8, 2015

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.

Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

April 6, 2015

Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. Yeast expressing a pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

Understanding structure, function, and mutations in the mitochondrial ATP synthase

March 24, 2015

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

March 20, 2015

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.