Vol. 02, 2015

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.

Yeast as a tool to explore cathepsin D function

H. Pereira¹, C.S.F. Oliveira^1,2, L. Castro¹, A. Preto¹, S. R. Chaves^1,#, M. Côrte-Real^1,#

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.

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.

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 Verlhac^1,2,3,4,5, Christophe Viret^1,2,3,4,5 and Mathias Faure^1,2,3,4,5

This microreview discusses the article "Autophagy Receptor NDP52 Regulates Pathogen-Containing Autophagosome Maturation" by Verlhac et al. (2015), Cell Host Microbe.

Struggling for breath in Sherbrooke: 1st Symposium on “One mitochondrion, many diseases” in Sherbrooke, Québec, Canada, March 11th, 2015

Ralf J. Braun^1,#, Verónica I. Dumit^2,3,#, Cécile Monpays⁴, Xavier Roucou⁵, Daniel Serrano⁶, Julie St-Pierre⁷, Paula J. Waters⁸, Ian Bates⁹, and Denis Gris¹⁰

This meeting report summarizes discussions during the "1st symposium on “One mitochondrion, many diseases," which took place in Sherbrooke in southern Québec in 2015.

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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.

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

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.

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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.

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

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.