Research, Research Articles
Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection
Tiago Monteiro-Brás1,2,3, Jordan Wesolowski1 and Fabienne Paumet1
This study reveals that the plasma membrane SNARE proteins SNAP-23 and Syntaxin 4 are crucial for Chlamydia trachomatis development by regulating lipid droplet homeostasis and supporting the formation of infectious progeny within host cells.
Yeast can express and assemble bacterial secretins in the mitochondrial outer membrane
Janani Natarajan1, Anasuya Moitra1, Sussanne Zabel1,§, Nidhi Singh2, Samuel Wagner2,3 and Doron Rapaport1
Secretins, essential components of bacterial secretion systems, can be expressed in yeast and show differential dependencies on mitochondrial import and assembly factors for membrane integration, suggesting diverse pathways for their assembly into the bacterial outer membrane.
Metabolic reprogramming of Salmonella infected macrophages and its modulation by iron availability and the mTOR pathway
Julia Telser1,2,#, Chiara Volani1,3,#, Richard Hilbe1,2, Markus Seifert1,2, Natascha Brigo1, Giuseppe Paglia4 and Günter Weiss1,2
This article shows that iron plays a critical role in both the immune response and metabolic reprogramming of macrophages during infection, influencing the TCA cycle and mTOR pathway, with implications for the growth of intracellular bacteria like Salmonella.
Transcriptomic and chemogenomic analyses unveil the essential role of Com2-regulon in response and tolerance of Saccharomyces cerevisiae to stress induced by sulfur dioxide
Patrícia Lage1,2, Belém Sampaio-Marques3,4, Paula Ludovico3,4, Nuno P. Mira5 and Ana Mendes-Ferreira1,2
This article shows that in the presence of sulfur dioxide (SO2), the transcription factor Com2 plays a critical role in the tolerance and response of Saccharomyces cerevisiae, affecting the expression of a majority of SO2-activated genes and contributing to the protection against stress induced by SO2 at an enologically relevant pH.
Network dynamics of the yeast methyltransferome
Guri Giaever1, Elena Lissina1 and Corey Nislow1
This article presents a systematic genetic analysis of methyltransferases (MTases) under normal and stress conditions, uncovering the complex and adaptive nature of the methyltransferome and discovering a potential connection between phospholipid methylation and histone methylation, suggesting interplay between lipid homeostasis and epigenetic regulation.
Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase
Isaac Corcoles-Saez1, Jean-Luc Ferat2, Michael Costanzo3, Charles M. Boone3 and Rita S. Cha1
This article shows that the carbon source affects the abundance of ribonucleotide reductase (RNR) subunits in yeast, with a novel Mec1 signaling axis regulating Rnr3 independently of known DNA damage response pathways, and reveals Rnr3's unexpected role in mitochondrial function.
Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release
Alexandre Légiot1, Claire Céré1, Thibaud Dupoiron1, Mohamed Kaabouni1, Nadine Camougrand1 and Stéphen Manon1
This study investigated the role of Mitochondria-Associated Membranes (MAMs) in the regulation of apoptosis by analyzing the localization and function of the pro-apoptotic protein Bax in yeast, finding that disruption of MAMs by deletion of the MDM34 gene affects Bax's mitochondrial localization and the release of cytochrome c.
Genomic saturation mutagenesis and polygenic analysis identify novel yeast genes affecting ethyl acetate production, a non-selectable polygenic trait
March 18, 2016
Isolation of mutants in populations of microorganisms has been a valuable tool in experimental genetics for decades. The main disadvantage, however, is the inability of isolating mutants in non-selectable polygenic traits. Our study shows that genomic saturation mutagenesis combined with complex trait polygenic analysis could be used successfully to identify causative alleles underlying many non-selectable, polygenic traits in small collections of haploid strains with multiple induced mutations.
Differentiated cytoplasmic granule formation in quiescent and non-quiescent cells upon chronological aging
March 3, 2016
Stationary phase cultures represent a complicated cell population comprising at least two different cell types, quiescent (Q) and non-quiescent (NQ) cells. The authors show that the cell fate of NQ cells is largely irreversible even if they are allowed to reenter mitosis. Their results reveal that the formation of different granule structures may represent the early stage of cell type differentiation in yeast stationary phase cultures.
Mitochondrial proteomics of the acetic acid – induced programmed cell death response in a highly tolerant Zygosaccharomyces bailii – derived hybrid strain
January 22, 2016
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.
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.
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.
INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering
November 13, 2015
Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
November 11, 2015
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.
Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae
October 22, 2015
Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of...
DNA damage checkpoint adaptation genes are required for division of cells harbouring eroded telomeres
September 21, 2015
In budding yeast, telomerase and the Cdc13p protein are two key players acting to ensure telomere stability. This article shows that while the capping process can be flexible, it takes a very specific genetic setup to allow a change from canonical capping to alternative capping.