Review, Reviews
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...
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.
Membrane depolarization-triggered responsive diversification leads to antibiotic tolerance
Natalie Verstraeten, Wouter Joris Knapen, Maarten Fauvart, Jan Michiels
In this article, the authors discuss the article "Obg and membrane depolarization are part of a microbial bet-hedging strategy that leads to antibiotic tolerance", Verstraeten et al., Mol. Cell 2015 Jul 2; 59 (1): 9-21.
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.
The interplay between transcription and mRNA degradation in Saccharomyces cerevisiae
July 3, 2017
This review summarizes how the integration of mRNA synthesis and degradation, mediated by specialized promoters and "coordinators," shapes the cellular transcriptome and plays a significant role in regulating gene expression profiles in various biological processes and potentially enhances evolutionary rates.
Inhibitors of glycosomal protein import provide new leads against trypanosomiasis
July 3, 2017
This article comments on work published by Dawidowski et al. (Science, 2017), which provides the grounds for further development of the glycosome inhibitors into clinical candidates and validates the parasite protein-protein interactions as drug targets.
Protein aggregation triggers a declining libido in elder yeasts that still have a lust for life
May 29, 2017
This article comments on work published by Schlissel et al (Science 2017), showing that aging in yeast does not lead to the expected loss of heterochromatin silencing due to Sir2 inactivity, but rather to reduced mating pheromone sensitivity caused by the aggregation of the RNA-binding protein Whi3, which can be reversed by eliminating Whi3's polyglutamine domain.
Post-transcriptional regulation of ribosome biogenesis in yeast
May 1, 2017
Microorganisms adapt to environmental changes by regulating their metabolism, and one key survival strategy is to decrease energy use during adverse conditions by halting ribosome production, with recent findings showing yeast can switch between pre-rRNA processing pathways in response to environmental shifts, adding complexity to ribosome biogenesis regulation.
Placeholder factors in ribosome biogenesis: please, pave my way
April 27, 2017
In ribosome synthesis, "placeholder" factors are crucial trans-acting elements that regulate the timing and assembly of ribosomal proteins, ensuring speed and accuracy in this intricate process by preventing premature interactions and guiding the proper formation of functional ribosomal subunits.
Insights from the redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains
April 25, 2017
This article comments on work published by Li et al. (PloS Pathog, 2017), focusing on Helicobacter pylori infections. They are mostly asymptomatic but can lead to serious conditions, and H. pylori lipopolysaccharide (LPS) is crucial for colonization and persistence, making the study of its structure and biosynthesis pathway vital for understanding pathogenesis and developing treatments.
Evading plant immunity: feedback control of the T3SS in Pseudomonas syringae
March 17, 2017
This article comments on work published by Waite et al. (mBio, 2017), which indicates that a negative autogenous control mechanism, where the sigma factor HrpL represses its own expression, permits the plant pathogen Pseudomonas syringae to fine-tune its type III secretion system, potentially reducing the elicitation of plant immunity and enhancing its ability to cause disease.
Microbial flora, probiotics, Bacillus subtilis and the search for a long and healthy human longevity
March 16, 2017
This article comments on work published by Donato et al. (Nat Commun, 2017), which reveals that the probiotic Bacillus subtilis extends the lifespan of Caenorhabditis elegans via mechanisms including the formation of biofilms and the production of signaling molecules like NO and CSF, suggesting a potential pathway through insulin-like signaling that could impact human longevity and age-related diseases.