Vol. 03, 2016
Bax mitochondrial relocation is linked to its phosphorylation and its interaction with Bcl-xL
David Garenne1,2, Thibaud T. Renault1,3, Stéphen Manon1
The heterologous expression of Bax, and other Bcl-2 family members, in the yeast Saccharomyces cerevisiae, has proved to be a valuable reporter system to investigate the molecular mechanisms underlying their interaction with mitochondria. Our data provide the molecular basis for a model of dynamic equilibrium for Bax localization and activation, regulated both by phosphorylation and Bcl-xL.
Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae
Santiago Cavero1,2, Esther Herruzo1, David Ontoso1,3 and Pedro A. San-Segundo1
In meiotic cells, the pachytene checkpoint or meiotic recombination checkpoint is a surveillance mechanism that monitors critical processes, such as recombination and chromosome synapsis, which are essential for proper distribution of chromosomes to the meiotic progeny. We report here that Sas2-mediated acetylation of histone H4 at lysine 16 (H4K16ac) modulates meiotic checkpoint activity in response to synaptonemal complex defects. Our results reveal that proper levels of H4K16ac orchestrate this meiotic quality control mechanism and that Sir2 impinges on additional targets to fully activate the checkpoint.
The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
Luna Laera1,#, Nicoletta Guaragnella1,#, Maša Ždralević1,¶, Domenico Marzulli1, Zhengchang Liu2 and Sergio Giannattasio1
Yeast Saccharomyces cerevisiae grown on glucose undergoes programmed cell death (PCD) induced by acetic acid (AA-PCD), but evades PCD when grown in raffinose. This is due to concomitant relief of carbon catabolite repression (CCR) and activation of mitochondrial retrograde signaling. In this work, we investigated the relationships between the RTG and CCR pathways in the modulation of AA-PCD sensitivity under glucose repression or de-repression conditions. Our data show that simultaneous mitochondrial retrograde pathway activation and SNF1-dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.
Autophagy: machinery and regulation
Zhangyuan Yin, Clarence Pascual and Daniel J. Klionsky
Macroautophagy/autophagy is an evolutionarily conserved cellular degradation process that targets cytoplasmic materials including cytosol, macromolecules and unwanted organelles. The discovery and analysis of autophagy-related (Atg) proteins have unveiled much of the machinery of autophagosome formation. In this review, we briefly summarize the physiological roles, molecular mechanism, regulatory network, and pathophysiological roles of autophagy.
Physiology, phylogeny, and LUCA
William F. Martin1,2, Madeline C. Weiss1, Sinje Neukirchen3, Shijulal Nelson-Sathi4, Filipa L. Sousa3
Genomes record their own history. But if we want to look all the way back to life's beginnings some 4 billion years ago, the record of microbial evolution that is preserved in prokaryotic genomes is not easy to read. The classical approach has been to look for genes that are universally distributed. Another approach is to make all trees for all genes, and sift out the trees where signals have been overwritten by lateral gene transfer. What is left ought to be ancient. If we do that, what do we find?
NprR, a moonlighting quorum sensor shifting from a phosphatase activity to a transcriptional activator
Stéphane Perchat1, Antoine Talagas2, Samira Zouhir2, Sandrine Poncet1, Laurent Bouillaut1,¶, Sylvie Nessler2 and Didier Lereclus1
This article comments on work published by Perchat et al. (PLoS Pathog, 2016), which demonstrates that, in the absence of the signaling peptide NprX, the sensor NprR is a dimer, which negatively controls sporulation in Bacillus thuringiensis, independently of its transcription factor activity.
The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription
Rubin Jiao1, Liubov Lobanova1, Amanda Waldner1, Anthony Fu1, Linda Xiao1, Troy A. Harkness1, and Terra G. Arnason1,2
The SNF1 kinase class of serine/threonine kinases, which includes the AMP-dependent protein kinase (AMPK) in other systems, are of widespread interest because of their important roles in glucose homeostasis, stress resistance, and aging. Our goal was to identify discrete ubiquitin-conjugating enzymes that are involved in SNF1 kinase activity in response to glucose levels and anticipated revealing those which are involved in Snf1-Ub attachment. Here, we report that the cell cycle and stress-related E2, Ubc1, indirectly affects SNF1 kinase activity not through stability, but through upstream events.
Threading Granules in Freiburg: 2nd International Symposium on “One Mitochondrion, Many Diseases – Biological and Molecular Perspectives”, a FRIAS Junior Researcher Conference, Freiburg im Breisgau, Germany, March 9th/10th, 2016
Ralf J. Braun1, Ralf M. Zerbes2, Florian Steinberg3, Denis Gris4, and Verónica I. Dumit5
INTRODUCTION Mitochondria (greek: μίτος & χονδρίον, mitos & chondrion, i.e., thread & granule) are the power houses of eukaryotic cells, and are pivotally involved in essential metabolic processes, including iron/sulfur
Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe
Jigang Wang1,2,# and Qingsong Lin2
This article comments on work published by Wang et al. (Nat Commun, 2014), which provides insights into the mode-of-action of artemisinin and its specificity against malaria parasites.
Translational repression in malaria sporozoites
Oliver Turque1, Tiffany Tsao1, Thomas Li1 and Min Zhang1,2
This article comments on work published by Zhang et al. (PLoS Pathog, 2016), which summarizea recent advances in the translational repression of gene expression in the malaria sporozoite.
Chromatin binding and silencing: Two roles of the same protein Lem2
Ramón Ramos Barrales and Sigurd Braun
This article comments on work published by Barrales et al. (Genes Dev, 2016), which identifies the nuclear envelope protein Lem2, a homolog of metazoan lamin-associated proteins (LAPs), as a relevant factor for heterochromatin silencing and perinuclear localization in the fission yeast Schizosaccharomyces pombe.
When and where? Pathogenic Escherichia coli differentially sense host D-serine using a universal transporter system to monitor their environment
James P. R. Connolly and Andrew J. Roe
This article comments on work published by Connolly et al. (PLoS Pathog, 2016), which describes the discovery of a functional and previously uncharacterized D-serine uptake system in E. coli.
Signaling pathways and posttranslational modifications of tau in Alzheimer’s disease: the humanization of yeast cells
Jürgen J. Heinisch1 and Roland Brandt2
In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. Substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. We give an overview on common modifications as they occur in tau during AD and discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells.
Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1
Laila Moustaq, Iwona I. Smaczynska-de Rooij, Sarah E. Palmer, Christopher J. Marklew, Kathryn R. Ayscough
The dynamins represent a superfamily of proteins that have been shown to function in a wide range of membrane fusion and fission events. An increasing number of mutations in the human classical dynamins, Dyn-1 and Dyn-2 has been reported, with diseases caused by these changes ranging from Charcot-Marie-Tooth disorder to epileptic encephalopathies. This study aimed to use the dynamin-like protein Vps1 of Saccharomyces cerevisiae as a model to gain insights into the mechanistic defects caused by specific dynamin mutations considered to underlie a number of diseases.
Hepatitis B virus and its sexually transmitted infection – an update
Takako Inoue1 and Yasuhito Tanaka1,2
About 5% of the world’s population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The purpose of this article is to provide up-to-date information on HBV and HBV infection as a major sexually transmitted infection.
Gonorrhea – an evolving disease of the new millennium
Stuart A. Hill, Thao L. Masters and Jenny Wachter
Neisseria gonorrhoeae (the gonococcus) is a Gram-negative diplococcus, an obligate human pathogen, and the etiologic agent of the sexually transmitted disease, gonorrhea. This review provides insight into the molecular epidemiology, virulence mechanisms, pathogenesis and therapeutic options.
Cryptococcus flips its lid – membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
Erika Shor1, Yina Wang1, David S. Perlin1,2, and Chaoyang Xue1,2
This article comments on work published by Huang et al. (MBio, 2016), which reported that in the pathogenic fungus Cryptococcus neoformans loss of lipid flippase activity sensitized cryptococcal cells to multiple classes of antifungal drugs and abolished fungal virulence in murine models.
A novel component of the mitochondrial genome segregation machinery in trypanosomes
Anneliese Hoffmann1,2, Martin Jakob1, and Torsten Ochsenreiter1
This article comments on work published by Trikin et al. (PLoS Pathog, 2016), which described a new component of the mitochondrial genome segregation machinery in the protozoan parasite Trypanosoma brucei.
Bacterial genotoxin functions as immune-modulator and promotes host survival
R. Guidi1, L. Del Bell Belluz2, T. Frisan2
This article comments on work published by Del Bel Belluz et al. (PLoS Pathog, 2016), which demonstrated that the typhoid toxin of Salmonella enterica serovar Typhi esembles an immune-modulatory molecule rather than a toxic agent.
Functions and regulation of the MRX complex at DNA double-strand breaks
Elisa Gobbini1, Corinne Cassani1, Matteo Villa1, Diego Bonetti2 and Maria Pia Longhese1
DNA double-strand breaks (DSBs) pose a serious threat to genome stability and cell survival. Cells possess mechanisms that recognize DSBs and promote their repair through either homologous recombination (HR) or non-homologous end joining (NHEJ). The present review focuses mainly on recent works in the budding yeast Saccharomyces cerevisiae to highlight structure and regulation of the evolutionary conserved Mre11-Rad50-Xrs2 (MRX) complex as well as its interplays with Tel1.
Inhibition of Zika virus by Wolbachia in Aedes aegypti
Eric Pearce Caragata, Heverton Leandro Carneiro Dutra and Luciano Andrade Moreira
This article comments on work published by Dutra et al. (Cell Host Microbe, 2016), which investigated the potential of Wolbachia infections in Aedes aegypti to restrict infection and transmission of Zika virus.
Syphilis: Re-emergence of an old foe
Lola V. Stamm
Syphilis is caused by infection with Treponema pallidum subsp. pallidum, a not-yet-cultivable spiral-shaped bacterium that is usually transmitted by sexual contact with an infected partner or by an infected pregnant woman to her fetus. This review provides insights into the etiology, epidemiology, clinical manifestation, diagnosis, treatment and prevention of syphilis.
Yeast screening platform identifies FDA-approved drugs that reduce Aβ oligomerization
Triana Amen1,2 and Daniel Kaganovich1
This article comments on work published by Park et al. (Microbial Cell, 2016), which discovered a number of small molecules capable of modulating Aβ aggregation in a yeast model.
Construction and evaluation of yeast expression networks by database-guided predictions
May 10, 2016
DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We set out to define a way to cluster microarray data according to their expressional relationship and to obtain information on the significance of this clustering approach.
Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii
May 1, 2016
Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Using an optogenetic sensor to monitor subcellular calcium in this model intracellular pathogen we found a novel regulatory function of phosphatidylthreonine in calcium signaling.
Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1
April 25, 2016
Candida albicans proliferates in two distinct cell types: blastopores and filaments. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We provide evidence that programmed cell death is cell-type specific in yeast: Filamentous C. albicans cells are more resistant to amphotericin B- and caspofungin-induced programmed cell death than their blastospore counterparts. Our genetic data suggest that this phenomenon is mediated by a protective mechanism involving the yeast metacaspase, MCA1.
A plant Bcl-2-associated athanogene is proteolytically activated to confer fungal resistance
April 16, 2016
This article comments on work published by Li et al. (Plant Cell, 2016), which focuses on the role of Bcl-2-associated athanogene 6 (BAG6) in plant innate immunity, showing that BAG6 plays a key role in basal plant defense against fungal pathogens.
The molecular and cellular action properties of artemisinins: what has yeast told us?
April 14, 2016
Artemisinin (ART) or Qinghaosu is a natural compound possessing superior anti-malarial activity. Although intensive studies have been done in the medicinal chemistry field to understand the structure-effect relationship, the biological actions of artemisinin are poorly understood and controversial. This review summarizes what we have learned from yeast about the basic biological properties of ARTs, as well as some key unanswered questions.
Formaldehyde fixation is detrimental to actin cables in glucose-depleted S. cerevisiae cells
April 13, 2016
Actin filaments form cortical patches and emanating cables in fermenting cells of Saccharomyces cerevisiae. We assume that stability of actin cables reflects the metabolic status of the cell. Based on comparison of live and formaldehyde-fixed cells, our data suggest that formaldehyde affects respiration before fixation and this uneven signaling results in destabilization of actin cables in glucose-deprived cells.
Non-genetic impact factors on chronological lifespan and stress resistance of baker’s yeast
April 13, 2016
This article comments on work published by Bisschops et al. (Microbial Cell, 2015), which illustrates how important the choice of the experimental setup is and how culture conditions influcence cellular aging and survival in biotechnological processes.
Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe
April 5, 2016
This article comments on work published by Wang et al. (Nat Commun, 2014), which provides insights into the mode-of-action of artemisinin and its specificity against malaria parasites.
Translational repression in malaria sporozoites
April 5, 2016
This article comments on work published by Zhang et al. (PLoS Pathog, 2016), which summarizea recent advances in the translational repression of gene expression in the malaria sporozoite.
Autophagy: one more Nobel Prize for yeast
Andreas Zimmermann1, Katharina Kainz1, Aleksandra Andryushkova1, Sebastian Hofer1, Frank Madeo1,2 and Didac Carmona-Gutierrez1
The recent announcement of the 2016 Nobel Prize in Physiology or Medicine, awarded to Yoshinori Ohsumifor the discoveries of mechanisms governing autophagy, underscores the importance of intracellular degradation and recycling. Here we provide a quick historical overview that mirrors both the importance of autophagy as a conserved and essential process for cellular life and death as well as the crucial role of yeast in its mechanistic characterization.