Research, Research Articles

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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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.

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

November 22, 2017

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

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.

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