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.
Ser/Thr protein phosphatases in fungi: structure, regulation and function
April 24, 2019
In this work we present the members of this family in S. cerevisiae and other fungal species, and review the most recent findings concerning their regulation and the roles they play in the most diverse aspects of cell biology.
Forty-five-year evolution of probiotic therapy
April 2, 2019
The field of probiotics has greatly expanded over the past 45 years, driven by the need for safer alternatives to drugs, interest in natural microbial products, and clinical proof of effectiveness, with scientific formulations increasingly defining the market and promising applications for various health areas expected in the future.
Role of pheromone recognition systems in creating new species of fission yeast
March 11, 2019
This article comments on work published by Seike at al. (PloS Biol., 2019), which demonstrated an “asymmetric” pheromone recognition system in the fission yeast Schizosaccharomyces pombe.
Adaptive bacterial response to low level chlorhexidine exposure and its implications for hand hygiene
March 7, 2019
This article shows that bacteria can adapt to low levels of Chlorhexidine digluconate (CHG), resulting in increased tolerance and cross-resistance to other antimicrobials, suggesting caution in the widespread use of CHG to minimize avoidable selection pressure for resistance.
Microevolution of the pathogenic yeasts Candida albicans and Candida glabrata during antifungal therapy and host infection
February 8, 2019
This review explores how Candida albicans and Candida glabrata, common fungal pathogens resistant to antifungal therapy, adapt and evolve within different environments, aiming to identify stable adaptive mechanisms as potential drug targets.
The extracellular matrix of mycobacterial biofilms: could we shorten the treatment of mycobacterial infections?
January 18, 2019
The article discusses the challenges presented by biofilms formed by non-tuberculous mycobacteria (NTM) species, which can lead to persistent infections that are difficult to treat due to phenotypic drug tolerance. The role of various cell wall components in mycobacterial biofilm formation is outlined, with a particular focus on Mycobacterium tuberculosis.
Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways
January 7, 2019
DNA recombination, repair and mutagenesis assays are powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.
Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes
January 7, 2019
Mechanistic assays of DNA repair processes are a powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.
Imbalance in gut microbes from babies born to obese mothers increases gut permeability and myeloid cell adaptations that provoke obesity and NAFLD
December 19, 2018
This article comments on work published by Soderborg et al. (Nat Commun, 2018), which demonstrates a causative role of early life microbiome dysbiosis in infants born to mothers with obesity in novel pathways that promote developmental programming of NAFLD.
Retroviral integration site selection: a running Gag?
November 19, 2018
In this article, the authors comment on the study "Structural basis for spumavirus GAG tethering to chromatin" by Lesbats et al. (Proc Natl Acad Sci, 2018) that revealed that the Gag protein of the spumaretrovirus prototype foamy virus (PFV) directly interacts with the nucleosome acidic patch, acting as a chromatin tether, and its disruption leads to delocalization of viral particles and integration sites, shedding light on the importance of retroviral structural proteins in the selection of integration sites.