Research, Research Reports

A versatile plasmid system for reconstitution and analysis of mammalian ubiquitination cascades in yeast

Rossella Avagliano Trezza1,#, Janny van den Burg1, Nico van den Oever1 and Ben Distel1,2

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

Lina Lindahl1, Samuel Genheden2, Fábio Faria-Oliveira1, Stefan Allard3, Leif A. Eriksson2, Lisbeth Olsson1, Maurizio Bettiga1,4

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.

Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin

Julia Ring1, Patrick Rockenfeller1, 3, Claudia Abraham1, Jelena Tadic1, Michael Poglitsch1, Katherina Schimmel1, 4, Julia Westermayer1, Simon Schauer1, Bettina Achleitner1, Christa Schimpel1, 5, Barbara Moitzi1, Gerald N. Rechberger1, 6, Stephan J. Sigrist7, 8, Didac Carmona-Gutierrez1, Guido Kroemer9, 10, 11, 12, 13, 14, 15, Sabrina Büttner1, 16, Tobias Eisenberg1, 2, Frank Madeo1, 2

This article indicates that spartin, a protein linked to hereditary spastic paraplegias, extends yeast lifespan and reduces age-related damage by associating with mitochondria and interacting with key metabolic proteins, implicating energy metabolism in its protective role during aging.

A genome-wide screen for FTY720-sensitive mutants reveals genes required for ROS homeostasis

Kanako Hagihara1, Kanako Kinoshita1, Kouki Ishida1, Shihomi Hojo1, Yoshinori Kameoka1, Ryosuke Satoh1, Teruaki Takasaki1 and Reiko Sugiura1

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.

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica

Jannell V. Bazurto1, Stephen P. Dearth2, Eric D. Tague2, Shawn R. Campagna2 and Diana M. Downs1

In Salmonella enterica, aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. Data herein describe the use of metabolomics to identify the metabolic state of mutant strains and probe the underlying mechanisms used by AICAR to inhibit thiamine synthesis. The results obtained provide a cautionary tale of using metabolite concentrations as the only data to define the physiological state of a bacterial cell.

The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development

Cletus A. Wezena1, Romy Alisch1, Alexandra Golzmann2, Linda Liedgens1, Verena Staudacher1,3, Gabriele Pradel2 and Marcel Deponte1,3

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

Clyde A. Smith1, Monolekha Bhattacharya2, Marta Toth2, Nichole K. Stewart2 and Sergei B. Vakulenko2

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

Petra Gottier1, Mauro Serricchio1, Rita Vitale2, Angela Corcelli2, and Peter Bütikofer1

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

Miguel Esteras1, I-Chun Liu1, Ambrosius P. Snijders2, Adam Jarmuz1 and Luis Aragon1

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.

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Valine biosynthesis in Saccharomyces cerevisiae is regulated by the mitochondrial branched-chain amino acid aminotransferase Bat1

March 21, 2018

In Saccharomyces cerevisiae, the yeast, the Bat1 and Bat2 proteins, which are branched-chain amino acid aminotransferases, play distinct roles in valine biosynthesis and cell growth regulation, with Bat1 primarily located in the mitochondria and Bat2 in the cytosol, and the mitochondria being identified as the major site of valine biosynthesis in this yeast.

Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor

March 7, 2018

Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. Here, Cabral et al. show that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity.

Impact of F1Fo-ATP-synthase dimer assembly factors on mitochondrial function and organismic aging

January 30, 2018

In aerobic organisms, mitochondrial F1Fo-ATP-synthase is the major site of ATP production. Here, Rampello et al. report on the role of the two dimer assembly factors PaATPE and PaATPG of the aging model Podospora anserina validating a model that links mitochondrial membrane remodeling to aging and identify specific molecular components triggering this process.

Yeast quiescence exit swiftness is influenced by cell volume and chronological age

December 6, 2017

Quiescence exit swiftness is crucial not only for micro-organisms in competition for an environmental niche, such as yeast, but also for the maintenance of tissue homeostasis in multicellular species. Here, Laporte et al. explore the effect of replicative and chronological age on Saccharomyces cerevisiae quiescence exit efficiency. Overall, their data illustrate that the quiescent state is a continuum evolving with time, early and deep quiescence being distinguishable by the cell’s proficiency to re-enter the proliferation cycle.

Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin

November 30, 2017

This article indicates that spartin, a protein linked to hereditary spastic paraplegias, extends yeast lifespan and reduces age-related damage by associating with mitochondria and interacting with key metabolic proteins, implicating energy metabolism in its protective role during aging.

The neuroprotective steroid progesterone promotes mitochondrial uncoupling, reduces cytosolic calcium and augments stress resistance in yeast cells

May 31, 2017

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

April 13, 2017

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.

The frequency of yeast [PSI+] prion formation is increased during chronological ageing

March 27, 2017

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

March 2, 2017

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).

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

December 2, 2016

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.