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.
The effect of multiple sclerosis therapy on gut microbiota dysbiosis: a longitudinal prospective study
April 6, 2024
The gut microbiota, a complex ecosystem with various immune functions, plays a significant role in MS, and its response to different treatments is highlighted in this study. In clinical practice, maintaining a healthy microbiota is crucial for individuals with MS.
Comparison of microbial communities and the profile of sulfate-reducing bacteria in patients with ulcerative colitis and their association with bowel diseases: a pilot study
March 14, 2024
Considerable evidence has accumulated regarding the molecular relationship between gut microbiota (GM) composition and the onset (clinical presentation and prognosis) of ulcerative colitis UC. Our findings highlight, among other observations, significant variations in the gut microbial composition among patients with varying disease severity and activity.
Replicative aging in yeast involves dynamic intron retention patterns associated with mRNA processing/export and protein ubiquitination
February 27, 2024
Saccharomyces cerevisiae has yielded relevant insights into some of the basic mechanisms of organismal aging. Among these are genomic instability, oxidative stress, caloric restriction and mitochondrial dysfunction. Our work uncovers a previously unexplored layer of the transcriptional program of yeast aging and, more generally, expands the knowledge on the occurrence of alternative splicing in baker´s yeast.
Predictable regulation of survival by intratumoral microbe-immune crosstalk in patients with lung adenocarcinoma
February 19, 2024
Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.
The last two transmembrane helices in the APC-type FurE transporter act as an intramolecular chaperone essential for concentrative ER-exit
January 5, 2024
FurE is a H+ symporter specific for the cellular uptake of uric acid, allantoin, uracil, and toxic nucleobase analogues in the fungus Aspergillus nidulans. Being member of the NCS1 protein family, FurE is structurally related to the APC-superfamily of transporters.
Basal level of ppGpp coordinates Escherichia coli cell heterogeneity and ampicillin resistance and persistence
October 25, 2023
The universal stringent response alarmone ppGpp (guanosine penta and tetra phosphates) plays a crucial role in various aspects of fundamental cell physiology (e.g., cell growth rate, cell size) and thus bacterial tolerance to and survival of external stresses, including antibiotics. In tihs study, we discuss the fundamental role of basal level of ppGpp in regulating cell homogeneity and ampicillin persistence.