Research, Research Articles
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.
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.
Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes
December 28, 2017
Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. Saccharomyces cerevisiae has two FITM homologues and the presented results suggest that Scs3p and Yft2p as well as FITMs in general are lipid phosphatase/phosphotransferase (LPT) enzymes involved in an as yet unknown critical step in phospholipid metabolism.
A versatile plasmid system for reconstitution and analysis of mammalian ubiquitination cascades in yeast
December 5, 2017
In this article Avagliano Trezza et al. describe a versatile vector system that allows the reconstitution of specific ubiquitination cascades in the model eukaryote Saccharomyces cerevisae (baker’s yeast) that provides a versatile tool to study complex post-translational modifications in a cellular setting.
Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae : biophysical mechanisms and implications for acetic acid tolerance
December 1, 2017
Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes.
A genome-wide screen for FTY720-sensitive mutants reveals genes required for ROS homeostasis
November 27, 2017
Fingolimod hydrochloride (FTY720) is an immune modulator for multiple sclerosis that also induces cancer cell apoptosis through reactive oxygen species generation, with a new study using fission yeast uncovering a gene network related to ROS homeostasis as a possible mechanism of FTY720's toxicity.
The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development
November 20, 2017
In this study the authors demonstrate that, PfGlo1 and PfcGlo2 are dispensable during asexual blood-stage development while the loss of PfcGlo2 may induce the formation of transmissible gametocytes. These combined data show that PfGlo1 and PfcGlo2 are most likely not suited as targets for selective drug development against the malaria parasite Plasmodium falciparum.
Aminoglycoside resistance profile and structural architecture of the aminoglycoside acetyltransferase AAC(6’)-Im
November 9, 2017
AAC(6')-Im, a monofunctional acetyltransferase, imparts increased resistance to certain aminoglycosides compared to its bifunctional homolog AAC(6')-Ie, with structural studies revealing differences in substrate binding that explain the discrepancies in their enzymatic activity and resistance profiles.
Cross-species complementation of bacterial- and eukaryotic-type cardiolipin synthases
November 3, 2017
This article shows that cardiolipin is crucial for cellular respiration and membrane integrity, with cardiolipin synthase enzymes like TbCLS in Trypanosoma brucei being potential drug targets due to their essential role in survival. The study demonstrates TbCLS's ability to restore cardiolipin production in yeast, highlighting the specificity and potential co-localization required for cardiolipin synthesis and remodeling, and underscoring the differences between eukaryotic and prokaryotic cardiolipin synthase mechanisms.
Identification of SUMO conjugation sites in the budding yeast proteome
October 2, 2017
The authors present a proteomic study that mapped SUMO acceptor lysines in budding yeast, identifying 257 potential conjugation sites, including both known and novel substrates, and providing a significant resource for future research into the functional implications of SUMOylation in yeast.
Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2
October 2, 2017
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.