Research, Research Articles
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.
The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription
Rubin Jiao1, Liubov Lobanova1, Amanda Waldner1, Anthony Fu1, Linda Xiao1, Troy A. Harkness1, and Terra G. Arnason1,2
The SNF1 kinase class of serine/threonine kinases, which includes the AMP-dependent protein kinase (AMPK) in other systems, are of widespread interest because of their important roles in glucose homeostasis, stress resistance, and aging. Our goal was to identify discrete ubiquitin-conjugating enzymes that are involved in SNF1 kinase activity in response to glucose levels and anticipated revealing those which are involved in Snf1-Ub attachment. Here, we report that the cell cycle and stress-related E2, Ubc1, indirectly affects SNF1 kinase activity not through stability, but through upstream events.
Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets
January Weiner 3rd1 and Taco W.A. Kooij2
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites.
VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast
Dário Trindade1,2, Clara Pereira3,4, Susana R. Chaves1, Stéphen Manon2, Manuela Côrte-Real1 and Maria João Sousa1
Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. In this study, we sought to determine whether Por1p functionally interacts with ADP/ATP carrier (AAC) proteins, as well as its contribution to cytochrome c release and yeast apoptosis induced by acetic acid treatment. Our data indicate that Por1p may regulate cell survival by acting as a negative regulator of AAC proteins in the apoptotic cascade.
Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging
Andrea L. Ruetenik1,2,3, Alejandro Ocampo1,2,3,¶, Kai Ruan4,5,#, Yi Zhu4,5, Chong Li4,6, R. Grace Zhai1,4,5,6 and Antoni Barrientos1,2,3,5
Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We could shown that enhancement of mitochondrial biogenesis protects against neurodegeneration in HD yeast and fly models. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.
Fecal gelatinase does not predict mortality in patients with alcohol-associated hepatitis
August 26, 2024
This study aimed to investigate the significance of fecal gelatinase on clinical outcomes in patients with alcohol-associated hepatitis. In conclusion, in our cohort, fecal gelatinase does not predict mortality and does not indicate higher disease severity in patients with alcohol-associated hepatitis.
Promoter methylation and increased expression of PD-L1 in patients with active tuberculosis
July 29, 2024
The PD-1/PD-L1 pathway plays a pivotal role in T cell activity and is involved in the pathophysiology of tuberculosis. Here we show that PD-L1 expression is increased in patients with active tuberculosis and is correlated with treatment outcomes.
Quantification methods of Candida albicans are independent irrespective of fungal morphology
July 26, 2024
Our study demonstrated that the quantification methods of C. albicans (cells/mL, CFU/mL, and vPCR) did not agree, regardless of the fungal morphology/growth, even though a significant and strong correlation is observed.
Pathogenic Escherichia coli change the adhesion between neutrophils and endotheliocytes in the experimental bacteremia model
July 22, 2024
In this work, we have demonstrated that in the model of experimental septicemia there is a disruption of adhesion contacts between neutrophils and endothelial cells, manifested by a decrease in adhesion force and work upon exposure to E. coli.
Arsenite treatment induces Hsp90 aggregates distinct from conventional stress granules in fission yeast
July 19, 2024
Given the conserved role of Hsp90 as a molecular chaperone protein, our findings presented in this study may suggest a novel type of arsenite-induced biological condensates, wherein Hsp90 plays a key role in maintaining its integrity.
Polyadenylated versions of small non-coding RNAs in Saccharomyces cerevisiae are degraded by Rrp6p/Rrp47p independent of the core nuclear exosome
May 22, 2024
In this investigation, we unveiled a novel functional role of the major nuclear 3′→5′ exoribonuclease, Rrp6p, and its cofactor Rrp47p in the degradation of polyadenylated versions of several mature sncRNAs, including 5S, 5.8S rRNAs, all sn- and some select snoRNAs in the baker’s yeast S. cerevisiae.
Exploring carbon source related localization and phosphorylation in the Snf1/Mig1 network using population and single cell-based approaches
May 16, 2024
In this work we set out to explore the relationship between the subcellular localization and regulation of kinases in the context of carbon source signaling. The data presented in this paper reinforce the notion that not only the activation/inactivation of kinases but also their subcellular localization and that of their targets influence fate decisions in response to environmental changes.
A Modular Cloning Toolkit for the production of recombinant proteins in Leishmania tarentolae
April 30, 2024
Modular Cloning (MoClo) is based on libraries of standardized genetic parts that can be directionally assembled via Golden Gate cloning in one-pot reactions into transcription units and multigene constructs. We established a MoClo toolkit and exemplified its application for the production of recombinant proteins in L. tarentolae.