Research, Research Articles
Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2
Jinglin L. Xie2,#, Iryna Bohovych3,#, Erin O.Y. Wong2, Jean-Philippe Lambert4, Anne-Claude Gingras2,4, Oleh Khalimonchuk3,5,6, Leah E. Cowen2 and Michelle D. Leach1,2
The authors descibe the role of the Hsp40 chaperone Ydj1 in Candida albicans, noting its localization to the cytosol and mitochondrial membrane, its necessity for stress responses and filamentation, and its involvement in a protein interaction network related to co-chaperones, filamentation regulators, and mitochondrial processing peptidases, with a particular focus on the impact of Ydj1 on mitochondrial morphology, function, and the import of precursor proteins.
Farnesol inhibits translation to limit growth and filamentation in C. albicans and S. cerevisiae
Nkechi E. Egbe1,2, Tawni O. Dornelles1, Caroline M. Paget1, Lydia M. Castelli1,3 and Mark P. Ashe1
Farnesol, a quorum-sensing molecule, inhibits the switch from yeast to filamentous growth in Candida albicans by impeding translation initiation, differing from fusel alcohols that affect the initiation factor eIF2B, as it disrupts mRNA interaction with the ribosome and prevents preinitiation complex formation.
Cristae architecture is determined by an interplay of the MICOS complex and the F1FO ATP synthase via Mic27 and Mic10
Katharina Eydt1,2, Karen M. Davies3, Christina Behrendt4, Ilka Wittig1,5 and Andreas S. Reichert1,2,4,*
This article investigates the roles of MICOS subunits Mic27 and Mic10, revealing their antagonistic and cooperative interactions in crista junction formation and cristae membrane curvature, and proposes a model where F1FO-ATP synthase is connected to MICOS, influencing CJ formation.
Integrative modules for efficient genome engineering in yeast
Triana Amen1 and Daniel Kaganovich1
The study introduces a set of vectors with integrative modules designed for effective genome integration into standard marker loci of Saccharomyces cerevisiae, enabling precise expression levels using various promoters and demonstrating the capability of stable multi-gene integration, which is useful for tasks like multi-color cellular imaging and metabolic engineering.
The neuroprotective steroid progesterone promotes mitochondrial uncoupling, reduces cytosolic calcium and augments stress resistance in yeast cells
Slaven Stekovic1,*, Christoph Ruckenstuhl1,*, Philipp Royer1, Christof Winkler-Hermaden1, Didac Carmona-Gutierrez1, Kai-Uwe Fröhlich1, Guido Kroemer3-8, and Frank Madeo1,2
Progesterone, known for its role in the reproductive system, also acts as a neurosteroid and has been suggested to aid recovery from traumatic brain injury; a study using yeast models shows that progesterone can protect against apoptosis, reduce oxidative stress and calcium spikes, and increase mitochondrial function, independent of traditional progesterone receptors or calcium transporters.
A simple microfluidic platform to study age-dependent protein abundance and localization changes in Saccharomyces cerevisiae
Margarita Cabrera1,†, Daniele Novarina1, Irina L. Rempel1, Liesbeth M. Veenhoff1, and Michael Chang1
We have developed a user-friendly microfluidic system paired with a genetic approach to enrich and study ageing mother yeast cells, enabling the monitoring of protein abundance and localization changes during the crucial first half of their replicative lifespan, leading to the discovery of novel age-dependent protein behaviors.
Thiol trapping and metabolic redistribution of sulfur metabolites enable cells to overcome cysteine overload
Anup Arunrao Deshpande1,#, Muskan Bhatia1,#, Sunil Laxman2, Anand Kumar Bachhawat1
In this study, researchers investigate the mechanisms for handling cysteine overload using Saccharomyces cerevisiae, finding that overexpressing the high affinity cysteine transporter, YCT1, enables yeast cells to rapidly accumulate high levels of intracellular cysteine. The study demonstrates that cells can manage potentially toxic levels of cysteine by converting it to non-reactive thiol forms and utilizing the metabolic products for cell growth.
The frequency of yeast [PSI+] prion formation is increased during chronological ageing
Shaun H. Speldewinde1 and Chris M. Grant1
Aging is marked by a decline in cellular functions and the increased formation of the yeast [PSI+] prion, an altered translation termination factor, which suggests that autophagy suppresses age-related prion development. Interestingly, yeast cells that adopt the [PSI+] form exhibit better survival through aging, indicating that [PSI+] formation, linked to enhanced autophagy, may confer advantages such as reduced protein aggregation and improved cell viability.
A multigene family encoding surface glycoproteins in Trypanosoma congolense
Magali Thonnus1, Amandine Guérin1,2 and Loïc Rivière1
Trypanosoma congolense, the causative agent of the most important livestock disease in Africa, expresses specific surface proteins involved in its parasitic lifestyle. By mining the T. congolense genome database, we identified a novel family of lectin-like glycoproteins (TcoClecs).
A modular cloning (MoClo) toolkit for reliable intracellular protein targeting in the yeast Saccharomyces cerevisiae
February 28, 2023
In this study, we describe an advanced Molecular cloning toolkit that is designed for the baker’s yeast Saccharomyces cerevisiae and optimized for the targeting of proteins of interest to specific cellular compartments.
The first taxonomic and functional characterization of human CAVD-associated microbiota
January 13, 2023
Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process. In this study, we aimed to investigate and characterize the presence of valvular microbiota and the associated immune response in human CAV samples originating from two European populations.
Cellular cholesterol licenses Legionella pneumophila intracellular replication in macrophages
December 6, 2022
Host membranes are inherently critical for niche homeostasis of vacuolar pathogens such as Legionella. One membrane component that is often subverted by vacuolar bacteria is cholesterol. We provide experimental evidence that cellular cholesterol promotes L. pneumophila replication within a membrane bound organelle in infected macrophages.
DadY (PA5303) is required for fitness of Pseudomonas aeruginosa when growth is dependent on alanine catabolism
November 22, 2022
Pseudomonas aeruginosa inhabits diverse environmental niches that can have varying nutrient composition. The ubiquity of this organism is facilitated by a metabolic strategy that preferentially utilizes low-energy, non-fermentable organic acids, such as amino acids, rather than the high-energy sugars preferred by many other microbes. The amino acid alanine is among the preferred substrates of P. aeruginosa. The dad locus encodes the constituents of the alanine catabolic pathway of P. aeruginosa. Physiological roles for DadR (AsnC-type transcriptional activator), DadX (alanine racemase), and DadA (D-amino acid dehydrogenase) have been defined in this pathway. An additional protein, PA5303, is encoded in the dad locus in P. aeruginosa. PA5303 is a member of the ubiquitous Rid protein superfamily and is designated DadY based on the data presented herein. (...)
Multiple genome analysis of Candida glabrata clinical isolates renders new insights into genetic diversity and drug resistance determinants
October 13, 2022
The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as Candida species. Candida glabrata ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as PDR1 (azole resistance) or FKS1/2 (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of C. glabrata drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The(...)
Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles
July 15, 2022
Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between membranes and contribute to longevity in different manners. We previously found that a 2-fold up-regulation of Osh6, one of seven yeast oxysterol-binding proteins, remedies vacuolar morphology defects in mid-aged cells, partly down-regulates the target of rapamycin complex 1 (TORC1), and increases the replicative lifespan. At the molecular level, Osh6 transports phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI4P) between the endoplasmic reticulum (ER) and the plasma membrane (PM). To decipher how an ER-PM working protein controls vacuolar morphology, we tested genetic interactions between OSH6 and DRS2, whose protein flips PS from the lumen to the cytosolic side of the Golgi, the organelle between ER and vacuoles in many pathways. Up-regulated (...)
Air- and dustborne fungi in repositories of the National Archive of the Republic of Cuba
April 1, 2022
This study has as objectives to determine the concentration and diversity of the air- and dustborne mycobiota in seven National Archive of the Republic of Cuba repositories, and to assess the potential risk of biodeterioration that iso-lated taxa may have. In the indoor and outdoor environmental microbiological samplings a SAS biocollector was used and the indoor/outdoor (I/O) ratio was determined for each repository. The settled dust was collected during six months. Sørensen's coefficient of similarity (QS) was calculated to compare the isolated taxa among the three studied niches (indoor air, dust, outdoor air). The biodegradation potential of the isolated taxa was determined by semi-quantitative tests. The concentrations in the air of repositories with natural cross-ventilation ranged from 225.2-750.3 CFU m-3, while in the Map library with air-conditioning (...)
Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability
January 31, 2022
Topoisomerase 1 (Top1) removes transcription-associated helical stress to suppress G4-formation and its induced recombination at genomic loci containing guanine-run containing sequences. Interestingly, Top1 binds tightly to G4 structures, and its inhibition or depletion can cause elevated instability at these genomic loci. Top1 is targeted by the widely used anti-cancer chemotherapeutic camptothecin (CPT) and its derivatives, which stabilize Top1 covalently attached on a DNA nick and prevent the re-ligation step. Here we investigated how CPT-resistance conferring Top1 mutants, which emerge in cancer patients and cells treated with CPT, affect G4-induced genomic instability in S. cerevisiae. We found that Top1 mutants form stable complexes with G4 DNA and that expression of Top1 cleavage-defective mutants but not a DNA-binding-defective (...)
Chromosome-condensed G1 phase yeast cells are tolerant to desiccation stress
November 26, 2021
The budding yeast Saccharomyces cerevisiae is capable of surviving extreme water loss for a long time. However, less is known about the mechanism of its desiccation tolerance. In this study, we revealed that in an exponential culture, all desiccation tolerant yeast cells were in G1 phase and had condensed chromosomes. (...)