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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From the baker to the bedside: yeast models of Parkinson’s disease

Regina Menezes^1,2, Sandra Tenreiro^3,5, Diana Macedo², Cláudia N. Santos^1,2, Tiago Fleming Outeiro^4,5,6

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.

In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor

Anne Silvestre^{1, 2, 3, 4}, Aurélie Plaze^{1, 2}, Patricia Berthon^{3, 4}, Roman Thibeaux^{1, 2}, Nancy Guillen^{1, 2} and Elisabeth Labruyère^{1, 2}

Background: Entamoeba histolytica cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction). The tissue inflammation associated with tumour necrosis factor (TNF) secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for E. histolytica, and the parasite may have a TNF receptor at its cell surface. Methods: confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and E. histolytica. Results: an antibody against human TNF receptor 1 (TNFR1) stained the E. histolytica trophozoite...

Evolutionary rewiring of bacterial regulatory networks

Tiffany B. Taylor^1,*, Geraldine Mulley¹, Liam J. McGuffin¹, Louise J. Johnson¹, Michael A. Brockhurst², Tanya Arseneault^1,3, Mark W. Silby⁴ and Robert W. Jackson^1,5

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.

Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast

Natalie K. Jones^1,2,4,#, Nagla T.T. Arab^1,3,#, Rawan Eid^1,3,#, Nada Gharib^1,5, Sara Sheibani^1,2,6, Hojatollah Vali², Chamel Khoury¹, Alistair Murray^1,2, Eric Boucher², Craig A. Mandato², Paul G. Young³ and Michael T. Greenwood¹

The human Thyroid Cancer-1 (hTC-1) protein, also known as C8orf4 was initially identified as a gene that was up-regulated in human thyroid cancer. This article reports that hTC-1 is a peptide that prevents the effects of over-expressing Bax in yeast. In sum, the results indicate that hTC-1 is a pro-survival protein that retains its function when heterologously expressed in yeast. Thus yeast is a useful model to characterize the potential roles in cell death and survival of cancer related genes.

Wanted Plasmodium falciparum, dead or alive

Fatimata Sow¹, Mary Nyonda¹, Anne-Lise Bienvenu^{1, 2}, Stephane Picot^{1, 2}

In this article, mechanisms of cell death in unicellular parasites are discussed, focussing on “programmed cell death” in Plasmodium.

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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 Herrero^1,* 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. Braun^1,#, Cornelia Sommer^2,3,#, Christine Leibiger^1,#, Romina J.G. Gentier^4,#, Verónica I. Dumit⁵, Katrin Paduch¹, Tobias Eisenberg², Lukas Habernig², Gert Trausinger⁶, Christoph Magnes⁶, Thomas Pieber^6,7, Frank Sinner^6,7, Jörn Dengjel⁵, Fred W. van Leeuwen⁴, Guido Kroemer^8-11, and Frank Madeo^2,3

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

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

Live fast, die soon: cell cycle progression and lifespan in yeast cells

Javier Jiménez, Samuel Bru, Mariana PC Ribeiro and Josep Clotet

Yeast as a tool for studying proteins of the Bcl-2 family

Peter Polčic, Petra Jaká and Marek Mentel

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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.

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 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).

A single mutation in the 15S rRNA gene confers non sense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria

August 2, 2015

This article presents the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. A hypothetical mechanism of suppression by "ribosome shifting" is also discussed in view of the nature of mutations suppressed and not suppressed.

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

July 30, 2015

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

July 30, 2015

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...

The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei

July 30, 2015

Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization. We measured drug concentrations that inhibit cell proliferation by 50% (IC50) for several compounds, chosen based on their lysosomotropic effects previously reported in Plasmodium falciparum. The lysosomal effects and cell death induced by L-leucyl-L-leucyl methyl ester (LeuLeu-OMe) were further analyzed by flow cytometry and immunofluorescence analyses of different lysosomal markers...

Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast

June 25, 2015

Wanted Plasmodium falciparum, dead or alive

June 23, 2015

In this article, mechanisms of cell death in unicellular parasites are discussed, focussing on “programmed cell death” in Plasmodium.

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