Research, Research Articles
Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes
Figarella K1, Marsiccobetre S1, Arocha I1, Colina W2, Hasegawa M2,†, Rodriguez M2, Rodriguez-Acosta A3, Duszenko M4, Benaim G5, Uzcategui NL3
The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.
INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering
Donna Garvey Brickner, Robert Coukos and Jason H. Brickner
Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
Michael E. Bond1, Rachel Brown1, Charalampos Rallis3,4, Jürg Bähler3,4 and Sara E. Mole1,2,3
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.
Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae
Markus M.M. Bisschops1,3,#, Tim Vos1,#, Rubén Martínez-Moreno2,4, Pilar de la Torre Cortés1, Jack T. Pronk1, Pascale Daran-Lapujade1
Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of...
DNA damage checkpoint adaptation genes are required for division of cells harbouring eroded telomeres
Sofiane Y. Mersaoui, Serge Gravel, Victor Karpov, and Raymund J. Wellinger
In budding yeast, telomerase and the Cdc13p protein are two key players acting to ensure telomere stability. This article shows that while the capping process can be flexible, it takes a very specific genetic setup to allow a change from canonical capping to alternative capping.
The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway
Chunyan Jin#, Stephen K. Kim, Stephen D. Willis and Katrina F. Cooper
Oxidative stress stimulates the Rho1 GTPase, which in turn induces the cell wall integrity (CWI) MAP kinase cascade. CWI activation promotes stress-responsive gene expression through activation of transcription factors (Rlm1, SBF) and nuclear release and subsequent destruction of the repressor cyclin C. This study reports that, in response to high hydrogen peroxide exposure, or in the presence of constitutively active Rho1, cyclin C still translocates to the cytoplasm and is degraded in cells lacking Bck1, the MAPKKK of the CWI pathway.
Formyl-methionine as a degradation signal at the N-termini of bacterial proteins
Konstantin I. Piatkov1,3,#, Tri T. M. Vu1,#, Cheol-Sang Hwang2 and Alexander Varshavsky1
Varshavsky and colleagues solve a long-standing mystery in proteolysis! In bacteria, all nascent proteins bear the pretranslationally formed N-terminal formyl-methionine (fMet) residue. The fMet residue is cotranslationally deformylated by a ribosome-associated deformylase. The formylation of N-terminal Met in bacterial proteins is not strictly essential for either translation or cell viability. Moreover, protein synthesis by the cytosolic ribosomes of eukaryotes does not involve the formylation of N-terminal Met. What, then, is the main biological function of this metabolically costly, transient, and not strictly essential modification of N‑terminal Met, and why has Met formylation not been eliminated during bacterial evolution? One possibility is that the similarity of the formyl and acetyl groups, their identical locations in...
A single mutation in the 15S rRNA gene confers non sense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria
Ali Gargouri, Catherine Macadré and Jaga Lazowska
This article presents the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. A hypothetical mechanism of suppression by "ribosome shifting" is also discussed in view of the nature of mutations suppressed and not suppressed.
Genomic epidemiology of carbapenemase-producing Klebsiella pneumoniae circulating in a Chilean tertiary-care hospital (2021–2022): Molecular characterization, resistance-virulence convergence, and clinical associations
May 21, 2026
This study characterized carbapenem-resistant Kp (CR-Kp) strains isolated at the Hospital Clínico Universidad de Chile (HCUCH) 2021-2022 and explored associations with clinical characteristics.
TOR-dependent regulation of the yeast homolog of the juvenile Batten Disease-associated gene CLN3
March 11, 2026
This study identifies conditions and genes that induce BTN1 expression in yeast. We show that BTN1 expression is regulated by translational control and by the mTOR1 pathway. An understanding of when and why BTN1 expression will aid in understanding the expression of CLN3, which may be helpful in the treatment of this devastating disease.
Overcoming phagocytosis resistance of hypervirulent Klebsiella pneumoniae by directly targeting capsules
February 16, 2026
This study highlights a promising strategy for disarming hypervirulent K. pneumoniae by directly targeting its key virulence factors and provides novel insights into antibacterial therapeutic approaches against this clinically significant pathogen.
VapA/Scs2 sustains polarized growth in Aspergillus nidulans by maintaining AP-2-mediated apical endocytosis
February 5, 2026
To explore the functional significance of ER–PM contact sites in filamentous fungi, we identified and genetically characterized all Aspergillus nidulans proteins homologous to Snc2/VAP, Ist2, or tricalbins.
Genetic make-up and regulation of the L-lysine biosynthesis pathway in Vibrio natriegens
February 3, 2026
This study analysed the make-up and regulation of the biosynthetic pathway for L-lysine and related L-aspartate family amino acids (AFAAs) in Vibrio natriegens DSM759 to provide a comprehensive basis for future metabolic engineering endeavours aiming at developing this strain into an amino acid overproducer.
Regulation of extracellular vesicles for protein secretion in Aspergillus nidulans
January 28, 2026
This study reveals that Aspergillus nidulans boosts extracellular vesicle production when ER-trafficked enzymes are induced, uncovering how fungi remodel their secretome through vesicle-mediated secretion to adapt to changing environments and biofilm formation.
Transcriptomic response to different heme sources in Trypanosoma cruzi epimastigotes
January 23, 2026
This study uncovers how the Chagas disease parasite adapts to changes in heme, an essential molecule for its survival, providing transcriptional clues to heme metabolism and identifying a previously unreported heme-binding protein in T. cruzi.
Sir2 regulates selective autophagy in stationary-phase yeast cells
January 21, 2026
This study establishes Sir2 as a previously unrecognized regulator of selective autophagy during the stationary phase and highlight how cells dynamically control organelle degradation.