Research, Research Articles
Formaldehyde fixation is detrimental to actin cables in glucose-depleted S. cerevisiae cells
Pavla Vasicova1,#, Mark Rinnerthaler2, Danusa Haskova1, Lenka Novakova1, Ivana Malcova1, Michael Breitenbach2, Jiri Hasek1
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
Laila Moustaq, Iwona I. Smaczynska-de Rooij, Sarah E. Palmer, Christopher J. Marklew, Kathryn R. Ayscough
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.
Genomic saturation mutagenesis and polygenic analysis identify novel yeast genes affecting ethyl acetate production, a non-selectable polygenic trait
Tom Den Abt1,2, Ben Souffriau1,2, Maria R. Foulquié-Moreno1,2, Jorge Duitama3, and Johan M. Thevelein1,2
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
Hsin-Yi Lee1,3,†, Kuo-Yu Cheng2,3,†, Jung-Chi Chao3 and Jun-Yi Leu3
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.
Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity
Elizabeth B. Smith, Stephen K. Dolan, David A. Fitzpatrick, Sean Doyle and Gary W. Jones
Gliotoxin is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus. In order to produce gliotoxin the host organism needs to have evolved a self-protection mechanism. The authors demonstrate that the activity of a novel thiomethyltransferase is requiered for protection against exogenous gliotoxin and provide implications for understanding the evolution of gliotoxin self-protection mechanisms.
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.
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.
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.
Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection
December 3, 2019
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
November 19, 2019
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
November 14, 2019
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
September 30, 2019
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
July 9, 2019
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
May 20, 2019
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
March 15, 2019
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.
Chlamydia pneumoniae is present in the dental plaque of periodontitis patients and stimulates an inflammatory response in gingival epithelial cells
March 11, 2019
This study found that Chlamydia pneumoniae is present more frequently in the dental plaque of individuals with periodontal disease, can invade human gingival epithelial cells causing inflammatory responses, and may therefore be a contributing factor to periodontal disease and a potential indicator of risk.