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. Thiaville^1,2,3,4, Rachel Legendre⁴, Diego Rojas-Benítez⁵, Agnès Baudin-Baillieu⁴, Isabelle Hatin⁴, Guilhem Chalancon⁶, Alvaro Glavic⁵, Olivier Namy⁴, Valérie de Crécy-Lagard^1,3

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 M^2,†, 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.

Bax mitochondrial relocation is linked to its phosphorylation and its interaction with Bcl-xL

David Garenne^1,2, Thibaud T. Renault^1,3, 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.

Autophagy: one more Nobel Prize for yeast

Andreas Zimmermann¹, Katharina Kainz¹, Aleksandra Andryushkova¹, Sebastian Hofer¹, Frank Madeo^1,2 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.

Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae

Santiago Cavero^1,2, Esther Herruzo¹, David Ontoso^1,3 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 Laera^1,#, Nicoletta Guaragnella^1,#, Maša Ždralević^1,¶, 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. Martin^1,2, 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?

Autophagy: machinery and regulation

Zhangyuan Yin, Clarence Pascual and Daniel J. Klionsky

NprR, a moonlighting quorum sensor shifting from a phosphatase activity to a transcriptional activator

Stéphane Perchat¹, Antoine Talagas², Samira Zouhir², Sandrine Poncet¹, Laurent Bouillaut^1,¶, 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.

Threading Granules in Freiburg: 2^nd International Symposium on “One Mitochondrion, Many Diseases – Biological and Molecular Perspectives”, a FRIAS Junior Researcher Conference, Freiburg im Breisgau, Germany, March 9^th/10^th, 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

The interaction between herpes simplex virus 1 genome and promyelocytic leukemia nuclear bodies (PML-NBs) as a hallmark of the entry in latency

Patrick Lomonte

This article comments on work published by Maroul et al. (PLoS Pathog, 2016), which demonstrates that the interaction of the viral genomes with the nuclear architecture and specifically the promyelocytic leukemia nuclear bodies is a major determinant for the entry of HSV-1 into latency.

Francisella IglG protein and the DUF4280 proteins: PAAR-like proteins in non-canonical Type VI secretion systems?

Claire Lays^{1, 2}, Eric Tannier^{2, 3}, Thomas Henry^1,2

This article comments on work published by Rigard et al. (PLoS Pathog, 2013), which identified the function of IgIG, a protein of unknown function, encoded within the Francisella Pathogenicity Island.

B cell-helping functions of gut microbial metabolites

Chang H. Kim^1,2,3,4

This article comments on work published by Kim et al. (Cell Host & Microbe, 2016), which showed that the microbial metabolites short-chain fatty acids (SCFAs) regulate the metabolism and gene expression in B cells to promote antibody production.

How do yeast sense mitochondrial dysfunction?

Dmitry A. Knorre¹, Svyatoslav S. Sokolov¹, Anna N. Zyrina², Fedor F. Severin^1,3

Apart from energy transformation, mitochondria play important signaling roles. In yeast, mitochondrial signaling relies on several molecular cascades. However, it is not clear how a cell detects a particular mitochondrial malfunction. In our review we argue that in yeast the major known routes of mitochondrial signaling are moderated by non-mitochondrial inputs.

Chlamydia trachomatis Genital Infections

Catherine M. O’Connell and Morgan E. Ferone

Chlamydia trachomatis infections are the most commonly reported sexually transmitted bacterial infections in the US and globally. Ascending infection may result in infertility, ectopic pregnancy and chronic pelvic pain in some women. In this review we provide an overview of current knowledge regarding epidemiology, disease outcomes and effective treatment of chlamydial genital tract infection and explore potential mechanisms facilitating C. trachomatis infection of genital mucosa identified via bioinformatics and other molecular approaches.

HPV disease transmission protection and control

Neil D. Christensen

Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. In this review we present an overview of papillomavirus biology and propose a series of questions that provide a basis for discussion of some areas of interest that continue to represent important gaps in our knowledge in the HPV research field.

Yeast screening platform identifies FDA-approved drugs that reduce Aβ oligomerization

Triana Amen^1,2 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.

Inhibition of Aβ₄₂ oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs

January 18, 2016

The formation of small Aβ42 oligomers has been implicated as a toxic species in Alzheimer disease (AD). Here, we show that the mechanism of the PICALM, human AD risk factor, is likely to reduce the level of Aβ42 oligomers in cells. We screened FDA-approved drugs to identify candidates that prevent the formation of Aβ42 small oligomers using the yeast Aβ42-RF reporter system. We also showed that each of the drug hits counteract yeast and mammalian cell toxicity associated with Aβ42 small aggregates.

Biofilm assembly becomes crystal clear – filamentous bacteriophage organize the Pseudomonas aeruginosa biofilm matrix into a liquid crystal

December 31, 2015

This article comments on work published by Secor et al. (Host Cell & Microbe, 2015), which highlights a previously unknown role for filamentous Pf phage in organizing the P. aeruginosa biofilm matrix into a liquid crystalline structure. These findings help ground our understanding of biofilm formation within established paradigms of soft matter physics

Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca²⁺ release in Leishmania mexicana promastigotes

December 11, 2015