Research, Research Articles

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).

Identification of Ftr1 and Zrt1 as iron and zinc micronutrient transceptors for activation of the PKA pathway in Saccharomyces cerevisiae

Joep Schothorst1,2, Griet Van Zeebroeck1,2 and Johan M. Thevelein1,2

We now show that the yeast high-affinity iron transporter Ftr1 and high-affinity zinc transporter Zrt1 function as transceptors for the micronutrients iron and zinc. We show that replenishment of iron to iron-starved cells or zinc to zinc-starved cells triggers within 1-2 minutes a rapid surge in trehalase activity, a well-established PKA target.

Balanced CoQ6 biosynthesis is required for lifespan and mitophagy in yeast

Isabel González-Mariscal, Aléjandro Martín-Montalvo, Cristina Ojeda-González, Adolfo Rodríguez-Eguren, Purificación Gutiérrez-Ríos, Plácido Navas, and Carlos Santos-Ocaña

In brief, we show that, in yeast, Ptc7 modulates the adaptation to respiratory metabolism by dephosphorylating Coq7 to supply newly synthesized CoQ6, and by activating mitophagy to remove defective mitochondria at stationary phase, guaranteeing a proper CLS in yeast.

Mutational analysis of fructose-1,6-bis-phosphatase FBP1 indicates partially independent functions in gluconeogenesis and sensitivity to genotoxic stress

Ali Ghanem, Ana Kitanovic, Jinda Holzwarth, Stefan Wölfl

Our results support predicted vital roles of several fructose-1,6-bisphosphatase residues for enzymatic activity and led to the identification of residues indispensable for the MMS-sensitizing effect. Despite an overlap between these two properties, careful analysis revealed two mutations, Asn75 and His324, which decouple the enzymatic activity and the MMS-sensitizing effect, indicating two distinctive biological activities linked in this key gluconeogenesis enzyme.

The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe

Theodora Sideri1, Yoko Yashiroda2, David A. Ellis1, María Rodríguez-López1, Minoru Yoshida2, Mick F. Tuite3 & Jürg Bähler1

Ctr4 exhibits multiple features diagnostic of other fungal prions and is the first example of a prion in fission yeast. These findings suggest that transmissible protein-based determinants of traits may be more widespread among fungi.

Improvement of biochemical methods of polyP quantification

Samuel Bru1, Javier Jiménez1, David Canadell2,#, Joaquín Ariño2, Josep Clotet1

As the main output of this evaluation we propose a straightforward and robust procedure that can be used as gold standard protocol for cellular polyP purification and determination from unicellular organisms, thus providing consistency to measurements and facilitating inter-laboratory comparisons and biological interpretation of the results.

Bax mitochondrial relocation is linked to its phosphorylation and its interaction with Bcl-xL

David Garenne1,2, Thibaud T. Renault1,3, Stéphen Manon1

The heterologous expression of Bax, and other Bcl-2 family members, in the yeast Saccharomyces cerevisiae, has proved to be a valuable reporter system to investigate the molecular mechanisms underlying their interaction with mitochondria. Our data provide the molecular basis for a model of dynamic equilibrium for Bax localization and activation, regulated both by phosphorylation and Bcl-xL.

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

Santiago Cavero1,2, Esther Herruzo1, David Ontoso1,3 and Pedro A. San-Segundo1

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 transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose

Luna Laera1,#, Nicoletta Guaragnella1,#, Maša Ždralević1,¶, Domenico Marzulli1, Zhengchang Liu2 and Sergio Giannattasio1

Yeast Saccharomyces cerevisiae grown on glucose undergoes programmed cell death (PCD) induced by acetic acid (AA-PCD), but evades PCD when grown in raffinose. This is due to concomitant relief of carbon catabolite repression (CCR) and activation of mitochondrial retrograde signaling. In this work, we investigated the relationships between the RTG and CCR pathways in the modulation of AA-PCD sensitivity under glucose repression or de-repression conditions. Our data show that simultaneous mitochondrial retrograde pathway activation and SNF1-dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.

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Investigation of the acetic acid stress response in Saccharomyces cerevisiae with mutated H3 residues

August 18, 2023

Yeast cells respond to acetic acid in diverse ways. Here, we have elucidated the deleterious effects of acetic acid on different histone mutants

The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella

August 17, 2023

Here we investigated why 5,6-dimethylbenzimidazole (DMB) inhibits in S. Typhimurium. Briefly, we determined that the structural similarities of the substituted benzene ring of DMB with the isoalloxazine moiety of flavins is responsible for the deleterious effects of this CoB12 precursor.

Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2

August 8, 2023

We show here that apart from its effector role for Elongator-dependent tRNA modification in yeast, Kti13 alias Dph8 also operates in step one of the diphthamide modification pathway.

Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates

July 10, 2023

Caspase 3 activation is a hallmark of cell death and there is a strong correlation between elevated protease activity and evolving pathology in neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS). These results suggest that caspase 3 is not inherently pathogenic, but may act as a compensatory proteostasis factor, to limit TDP-43 protein inclusions and protect organelle function in aggregation related degenerative disease.

Metallothionein Cup1 attenuates nitrosative stress in the yeast Saccharomyces cerevisiae

July 10, 2023

Our findings suggest that the yeast metallothionein Cup1 contributes to nitrosative stress tolerance, possibly as a constitutive rather than an inducible defense mechanism.

GFP fusions of Sec-routed extracellular proteins in Staphylococcus aureus reveal surface-associated coagulase in biofilms

June 28, 2023

We show that msfGFP can be used to generate extracellular fluorescent fusion proteins in S. aureus, applicable for proteins that are secreted through the Sec pathway. When fused to coagulase, msfGFP did not hinder the biological function, and the fusion protein localised to the fibrin pseudocapsule surrounding clusters of S. aureus cells.

Atg1, a key regulator of autophagy, functions to promote MAPK activation and cell death upon calcium overload in fission yeast

May 10, 2023

Here, we provide evidence that the fission yeast Atg1 regulates cell death responses upon intracellular calcium load in addition to its role in promoting Pmk1 MAPK.

Acetate modulates the inhibitory effect of Lactobacillus gasseri against the pathogenic yeasts Candida albicans and Candida glabrata

March 21, 2023

The results herein described advance the design of new anti-Candida therapies based on probiotics, in particular, those based on vaginal lactobacilli species, helping to reduce the significant burden that infections caused by Candida have today in human health.

D-Serine reduces the expression of the cytopathic genotoxin colibactin

March 8, 2023

Sensing and responding to environmental cues and signalling molecules is crucial for bacterial survival. In this study we have identified a D-amino acid that has a strong regulatory effect on the pks genomic island which encodes for biosynthesis genes for the genotoxic compound colibactin.

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