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.
Diverse conditions support near-zero growth in yeast: Implications for the study of cell lifespan
August 20, 2019
This review discusses alternative cultivation methods for baker's yeast to study its chronological lifespan, with the aim of better understanding the ageing of non-dividing cells and their potential implications for the lifespan of multicellular eukaryotes such as humans.
Evolution of the bacterial nucleosidase PpnN and its relation to the stringent response
July 16, 2019
This article comments on work published by Zhang et al (Mol Cell, 2019), which discovered an interesting mode of regulation of purine metabolism unique to Proteobacteria.
Integrins in disguise – mechanosensors in Saccharomyces cerevisiae as functional integrin analogues
July 15, 2019
This article shows that although yeast lack integrin-like proteins, they possess WSC- and MID-type mechanosensors that functionally resemble integrins in animal cells, playing a role in sensing external mechanical stimuli and activating the conserved PKC1-SLT1 cell wall integrity pathway, with potential implications for understanding mechanosensing in yeast biology.
Bacterial maze runners reveal hidden diversity in chemotactic performance
July 1, 2019
This article comments on work published by Salek et al. (Nat Commun, 2019), which combined microfluidic experiments with mathematical modeling to demonstrate that even in clonal populations, bacteria are individuals with different abilities to climb chemical gradients.
Laundry and textile hygiene in healthcare and beyond
July 1, 2019
This article shows that while institutional laundering is regulated to ensure hygiene, the trend towards energy-efficient washing at lower temperatures raises concerns about the antimicrobial efficacy of domestic laundering, with a focus on addressing microbial contamination in both clinical and home settings.
Bacterial pathogens under high-tension: Staphylococcus aureus adhesion to von Willebrand factor is activated by force
June 11, 2019
This article comments on work published by Viela et al (mBio, 2019), which shows that the bacterial cell surface protein A to the large plasma glycoprotein von Willebrand factor interaction is tightly regulated by mechanical force.
Yeast AP-1 like transcription factors (Yap) and stress response: a current overview
May 28, 2019
This review summarizes current understanding of the eight Yap transcription factors in Saccharomyces cerevisiae, detailing their activation by specific stress conditions and discussing their function and evolution across various fungal species.
Septin clearance from the division site triggers cytokinesis in budding yeast
May 22, 2019
This article comments on work published by Tamborrini et al (Nat Commun., 2019), which shows that septin displacement during splitting is an essential prerequisite for contractile actomyosin ring constriction during mitosis.
The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging
May 13, 2019
This article shows that the microbiota is crucial for immune system development and that its relationship with the immune system during aging and the pathogenesis of age-related diseases, including cancer, needs further research to inform disease treatment and prevention.