Research, Research Articles

Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells

Maxence de Taffin de Tilques1,$, Jean-Paul Lasserre1,$, François Godard1, Elodie Sardin1, Marine Bouhier1, Marina Le Guedard2,3, Roza Kucharczyk4, Patrice X. Petit5, Eric Testet2, Jean-Paul di Rago1, Déborah Tribouillard-Tanvier1,#

Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). Here, de Taffin de Tilques et al. describe that a diminished capacity of CL remodeling deficient cells to preserve protein homeostasis is likely an important factor contributing to the pathogenesis of Barth Syndrome (BTHS) and identifies cytosolic translation as a potential therapeutic target for the treatment of this disease.

Production of poly-β-1,6-N-acetylglucosamine by MatAB is required for hyphal aggregation and hydrophilic surface adhesion by Streptomyces

Dino van Dissel1, Joost Willemse1, Boris Zacchetti1, Dennis Claessen1, Gerald B. Pier2, Gilles P. van Wezel1

In this article van Dissel et al. describe new insights to allow better control of liquid-culture morphology of streptomycetes, which may be harnessed to improve growth and industrial exploitation of these highly versatile natural product and enzyme producers.

Impact of F1Fo-ATP-synthase dimer assembly factors on mitochondrial function and organismic aging

Nadia G Rampello1, Maria Stenger2, Benedikt Westermann2, Heinz D Osiewacz1

In aerobic organisms, mitochondrial F1Fo-ATP-synthase is the major site of ATP production. Here, Rampello et al. report on the role of the two dimer assembly factors PaATPE and PaATPG of the aging model Podospora anserina validating a model that links mitochondrial membrane remodeling to aging and identify specific molecular components triggering this process.

Non-canonical regulation of glutathione and trehalose biosynthesis characterizes non-Saccharomyces wine yeasts with poor performance in active dry yeast production

Esther Gamero-Sandemetrio1, Lucía Payá-Tormo1, Rocío Gómez-Pastor1,3, Agustín Aranda1,2 and Emilia Matallana1,2

Several yeast species, belonging to Saccharomyces and non-Saccharomyces genera, play fundamental roles during spontaneous must grape fermentation, and recent studies have shown that mixed fermentations, co-inoculated with S. cerevisiae and non-Saccharomyces strains, can improve wine organoleptic properties. Here, Gamero-Sandemetrio et al. present findings that non-canonical regulation of glutathione and trehalose biosynthesis could cause poor fermentative performance after active dry yeast (ADY) production, as it corroborates the corrective effect of antioxidant treatments, during biomass propagation, with both pure chemicals and food-grade argan oil.

Molecular signature of the imprintosome complex at the mating-type locus in fission yeast

Célia Raimondi1, Bernd Jagla2, Caroline Proux3, Hervé Waxin4, Serge Gangloff1, Benoit Arcangioli1

Genetic and molecular studies have indicated that an epigenetic imprint at mat1, the sexual locus of fission yeast, initiates mating type switching. Here, Raimondi et al. characterized the recruitment of early players of mating type switching at the mat1 region and suggest a nucleoprotein protective structure defined as imprintosome.

Leishmania guyanensis parasites block the activation of the inflammasome by inhibiting maturation of IL-1β

Mary-Anne Hartley1,¶, Remzi O. Eren1,¶, Matteo Rossi1, Florence Prevel1, Patrik Castiglioni1, Nathalie Isorce1, Chantal Desponds1, Lon-Fye Lye2, Stephen M. Beverley2, Stefan K. Drexler1,&, Nicolas Fasel1,&

The various symptomatic outcomes of cutaneous leishmaniasis relates to the type and potency of its underlying inflammatory responses mediated by Toll-Like-Receptor-3 (TLR3). Here, Hartely et al. investigated other innate pattern recognition receptors capable of reacting to dsRNA and potentially contributing to LRV1-mediated inflammatory pathology. They postulate that avoidance of the inflammasome pathways is likely an important mechanism of virulence in Leishmania infection irrespective of the LRV1-status.

A novel system to monitor mitochondrial translation in yeast

Tamara Suhm1, Lukas Habernig2, Magdalena Rzepka1, Jayasankar Mohanakrishnan Kaimal3, Claes Andréasson3, Sabrina Büttner2,3 and Martin Ott1

In this study Suhm et al. present a novel system to monitor mitochondrial translation by detection of mitochondrial GFP-translation through fluorescence microscopy and flow cytometry in functional mitochondria. This novel tool allows the investigation of the function and regulation of mitochondrial translation during stress signaling, aging and mitochondrial biogenesis.

Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes

Matthew J Hayes1, Vineet Choudhary2, Namrata Ojha2, John JH Shin3, Gil-Soo Han4, George M. Carman4, Christopher JR Loewen3, William A Prinz2 and Timothy P Levine1

Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. Saccharomyces cerevisiae has two FITM homologues and the presented results suggest that Scs3p and Yft2p as well as FITMs in general are lipid phosphatase/phosphotransferase (LPT) enzymes involved in an as yet unknown critical step in phospholipid metabolism.

Yeast quiescence exit swiftness is influenced by cell volume and chronological age

Damien Laporte1, Laure Jimenez1, Laëtitia Gouleme1, Isabelle Sagot1

Quiescence exit swiftness is crucial not only for micro-organisms in competition for an environmental niche, such as yeast, but also for the maintenance of tissue homeostasis in multicellular species. Here, Laporte et al. explore the effect of replicative and chronological age on Saccharomyces cerevisiae quiescence exit efficiency. Overall, their data illustrate that the quiescent state is a continuum evolving with time, early and deep quiescence being distinguishable by the cell’s proficiency to re-enter the proliferation cycle.

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

December 4, 2016

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 ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription

November 5, 2016

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.

Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets

August 30, 2016

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

August 25, 2016

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.

Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging

July 26, 2016

Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We could shown that enhancement of mitochondrial biogenesis protects against neurodegeneration in HD yeast and fly models. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.

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.

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.

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.

Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1

March 22, 2016

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.

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