Vol. 03, 2016
Histone modifications as regulators of life and death in Saccharomyces cerevisiae
Birthe Fahrenkrog
The mechanism by which chromosomes restructure during apoptosis is still poorly understood, but it is becoming increasingly clear that altered epigenetic histone modifications are fundamental parameters that influence the chromatin state and the nuclear rearrangements within apoptotic cells. This review highlights recent work on the epigenetic regulation of programmed cell death in budding yeast.
Spermidine cures yeast of prions
Shaun H. Speldewinde, and Chris M. Grant
This article comments on work published by Speldewinde and Grant (Mol Biol Cell, 2015), which found that spermidine, a polyamine that has been used to increase autophagic flux, acts as a protective agent which prevents spontaneous prion formation in yeast.
Global translational impacts of the loss of the tRNA modification t6A in yeast
Patrick C. Thiaville1,2,3,4, Rachel Legendre4, Diego Rojas-Benítez5, Agnès Baudin-Baillieu4, Isabelle Hatin4, Guilhem Chalancon6, Alvaro Glavic5, Olivier Namy4, Valérie de Crécy-Lagard1,3
The universal tRNA modification t6A is found at position 37 of nearly all tRNAs decoding ANN codons. Analysis of codon occupancy rates suggests that one of the major roles of t6A is to homogenize the process of elongation by slowing the elongation rate at codons decoded by high abundance tRNAs and I34:C3 pairs while increasing the elongation rate of rare tRNAs and G34:U3 pairs. This work reveals that the consequences of t6A absence are complex and multilayered and has set the stage to elucidate the molecular basis of the observed phenotypes.
Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes
Figarella K1, Marsiccobetre S1, Arocha I1, Colina W2, Hasegawa M2,†, Rodriguez M2, Rodriguez-Acosta A3, Duszenko M4, Benaim G5, Uzcategui NL3
The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.
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.
Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets
January Weiner 3rd1 and Taco W.A. Kooij2
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites.
VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast
Dário Trindade1,2, Clara Pereira3,4, Susana R. Chaves1, Stéphen Manon2, Manuela Côrte-Real1 and Maria João Sousa1
Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. In this study, we sought to determine whether Por1p functionally interacts with ADP/ATP carrier (AAC) proteins, as well as its contribution to cytochrome c release and yeast apoptosis induced by acetic acid treatment. Our data indicate that Por1p may regulate cell survival by acting as a negative regulator of AAC proteins in the apoptotic cascade.
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.
The bacterial cell cycle checkpoint protein Obg and its role in programmed cell death
Liselot Dewachter1, Natalie Verstraeten1, Maarten Fauvart1,2 and Jan Michiels1
This article comments on work published by Dewachter et al. (mBio, 2015), which identified a programmed cell death mechanism in Escherichia coli that is triggered by a mutant isoform of the essential GTPase ObgE.
Control of the gut microbiome by fecal microRNA
Shirong Liu and Howard L. Weiner
This article comments on work published by Liu et al. (Cell Host & Microbe, 2016), which identifies miRNAs in gut lumen and feces of both mice and humans that were able to enter bacteria, specifically regulate bacterial gene transcripts and affect bacterial growth thereby regulating the gut microbiome.
Mitochondrial regulation of cell death: a phylogenetically conserved control
Lorenzo Galluzzi1,2,3,4,5, Oliver Kepp1,2,3,4,6 and Guido Kroemer1,2,3,4,6,7,8
Mitochondria are fundamental for eukaryotic cells as they participate in critical catabolic and anabolic pathways. Moreover, mitochondria play a key role in the signal transduction cascades that precipitate many (but not all) regulated variants of cellular demise. In this short review, the authors discuss the differential implication of mitochondria in the major forms of regulated cell death.
Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis
June 30, 2016
Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. In this report, we describe the isolation of a robust suppressor of the respiratory defect in cox23∆ cells that mapped to the mitochondrial-encoded Cox1 subunit.
Inhibition of Zika virus by Wolbachia in Aedes aegypti
June 27, 2016
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
June 27, 2016
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.
Trichomoniasis – are we giving the deserved attention to the most common non-viral sexually transmitted disease worldwide?
June 27, 2016
Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease (STD) in the world. This article contributes to claim the attention of public health policies to control this STD.
House of cellulose – a new hideout for drug tolerant Mycobacterium tuberculosis
June 23, 2016
This article comments on work published by Trivedi et al. (Nat Commun, 2016), which shows that Mycobacterium tuberculosis cells organise themselves into biofilms in response to intracellular thiol reductive stress.
Antibiotic use in childhood alters the gut microbiota and predisposes to overweight
June 20, 2016
This article comments on work published by Korpela et al. (Nat Commun, 2016), which investigates the correlation between the use of antibiotics in early life and the excessive weight gain in later childhood.
Evidence for the hallmarks of human aging in replicatively aging yeast
June 20, 2016
Recently, efforts have been made to characterize the hallmarks that accompany and contribute to the phenomenon of aging, as most relevant for humans. Remarkably, studying the finite lifespan of the single cell eukaryote budding yeast has been paramount for our understanding of aging. Here, we compile observations from literature over the past decades of research on replicatively aging yeast to highlight how the hallmarks of aging in humans are present in yeast.
Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon
May 15, 2016
Ribonucleotides (rNMPs) can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. We report here that recombination is not stimulated by rNMPs incorporated by the replicative polymerase epsilon. Instead, recombination seems to be stimulated by multiple contiguous rNMPs, which may arise from R-loops or replication priming events.
Bacterial outer membrane vesicle biogenesis: a new mechanism and its implications
May 10, 2016
This article comments on work published by Roier et al. (Nat Commun, 2016), which proposes a novel and highly conserved bacterial outer membane vesicle biogenesis mechanism based on phospholipid accumulation in the outer leaflet of the outer membrane.
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.