Microreviews, Review
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 replication timing program in the hands of two HDACs
July 25, 2014
This article comments on work published by Yoshida et al. (Mol Cell, 2014), which performed a systematic analysis of the role of histone deacetylases (HDACs) in the regulation of origin activity in budding yeast, finding that the epigenetic regulation of repetitive sequences is a key determinant of the DNA replication program.
Increased Trypanosoma brucei cathepsin-L activity inhibits human serum-mediated trypanolysis
July 14, 2014
This article comments on work published by Alsford et al. (PLoS Pathogens, 2014), which identified a Trypanosoma brucei lysosomal cathepsin with an inhibitory effect on human serum’s trypanolytic action.
A novel role of centrin in flagellar motility: stabilizing an inner-arm dynein motor in the flagellar axoneme
July 14, 2014
This article comments on work published by Wei et al. (Nat Comm, 2014), which discovered that centrin maintains the stability of an inner-arm dynein in the flagellar axoneme in Trypanosoma brucei.
A non-proteolytic function of ubiquitin in transcription repression
July 6, 2014
This article comments on work published by Ndoja et al. (Mol Cell, 2014), which demonstrates that monoubiquitination of some transcription activators can inhibit transcription by recruiting the AAA+ ATPase Cdc48 (also known in metazoans as p97 or VCP), which then extracts the ubiquitinated activator from DNA.
Mutagenesis by host antimicrobial peptides: insights into microbial evolution during chronic infections
June 29, 2014
This article comments on work published by Limoli et al. ((PLoS Pathogens, 2014), which provides evidence that at subinhibitory levels, AMPs promote mutations in bacterial DNA, which enhance bacterial survival.
Where antibiotic resistance mutations meet quorum-sensing
June 25, 2014
This article comments on work published by Krašovec et al. (Nat Comm, 2014), which found that the modulation of de novo mutation to promote antibiotic resistance depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress).
Sphingolipids and mitochondrial function, lessons learned from yeast
June 25, 2014
This article reviews recent research showing that Saccharomyces cerevisiae is an invaluable model to investigate sphingolipids as signaling molecules in modulating mitochondrial function, but can also be used as a tool to further enhance our current knowledge on sphingolipids and mitochondria in mammalian cells.
Genome evolution in yeast reveals connections between rare mutations in human cancer
June 2, 2014
This article comments on work published by Teng et al. (Mol Cell, 2013), which, using the yeast knockout collections, provides hard evidence that single gene deletions/mutations in most non-essential genes can drive the selection for cancer-like mutations.
Decoding the biosynthesis and function of diphthamide, an enigmatic modification of translation elongation factor 2 (EF2)
May 20, 2014
This article comments on work published by Uthman et al. (PLoS Genet, 2013), which suggests that Dph5 has a novel role as an EF2 inhibitor that affects cell growth when diphthamide synthesis is blocked or incomplete and shows that diphthamide promotes the accuracy of EF2 performance during translation.