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
Mitochondrial proteomics of the acetic acid – induced programmed cell death response in a highly tolerant Zygosaccharomyces bailii – derived hybrid strain
Joana F Guerreiro1, Belém Sampaio-Marques2,3, Renata Soares4, Ana Varela Coelho4, Cecília Leão2,3, Paula Ludovico2,3, Isabel Sá-Correia1
Very high concentrations of acetic acid at low pH induce programmed cell death (PCD) in both the experimental model Saccharomyces cerevisiae and in Zygosaccharomyces bailii, the latter being considered the most problematic acidic food spoilage yeast due to its remarkable intrinsic resistance to this food preservative. This study offers insights into the mechanisms involved in acetic acid - induced PCD in the Z. bailii-derived hybrid strain ISA1307 by analyzing the yeast mitochondrial protein expression profile of cells challenged by acetic acid.
The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan in Saccharomyces cerevisiae
Ryo Higuchi-Sanabria1, Jason D. Vevea1,3, Joseph K. Charalel1,4, Maria L. Sapar5, Liza A. Pon1,2
Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan in C. elegans and S. cerevisiae. Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Here, we report that Sum1p and Sir2p inversely regulate actin and mitochondrial maintenance, as well as lifespan.
Learning epigenetic regulation from mycobacteria
Sanjeev Khosla1, Garima Sharma1,2 and Imtiyaz Yaseen1,2
This article comments on work published by Koshla et al. (Nat Commun, 2015), which shows that pathogenic Mycobacterium tuberculosis has evolved strategies to hijack the epigenetic regulation of host transcripton for its own survival.
Inhibition of Aβ42 oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs
Sei-Kyoung Park1, Kiira Ratia2, Mariam Ba1, Maria Valencik1 and Susan W. Liebman1,3
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
Patrick R. Secor1, Laura K. Jennings1, Lia A. Michaels1, Johanna M. Sweere2, Pradeep K. Singh1, William C. Parks3, Paul L. Bollyky2
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
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.
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.
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
Histone modifications as regulators of life and death in Saccharomyces cerevisiae
December 31, 2015
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
December 25, 2015
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
December 18, 2015
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
December 11, 2015
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.
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.