Vol. 04, 2017

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 new role for the nuclear basket network

Paola Gallardo1, Silvia Salas-Pino1 and Rafael R. Daga1

This article comments on work published by Salas-Pino et al. (J Cell Biol, 2017), which describes a novel function of the fission yeast nuclear basket component - the translocated promoter region (TPR) nucleoporin Alm1 - in proper localization of the proteasome to the nuclear envelope.

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.

VAMP8 mucin exocytosis attenuates intestinal pathogenesis by Entamoeba histolytica

Steve Cornick1, France Moreau1, Herbert Y. Gaisano2, Kris Chadee1

This article comments on work published by Cornick et al. (mBio, 2017), which nominates SNARE-mediated exocytosis as the putative mechanism responsible for pathogen-induced mucus secretion from goblet cells.

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.

Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase

Kaitlin A. Davis1 and John T. Patton2

This article comments on work published by Davis et al. (mBio, 2017), which describes molecular requirements that govern NSP1 recognition of β-TrCP, including an essential degron phosphorylation event, and the step-wise incorporation of NSP1 into hijacked cullin-RING E3 ligases (CRLs) that ubiquitinate and tag β-TrCP for degradation.

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.

Breaking the bad: Bacillus blocks fungal virulence factors

François L. Mayer1 and James W. Kronstad1

This article comments on work published by Mayer & Kronstad (mBio, 2017), which identified the soil bacterium, Bacillus safensis as a potent inhibitor of virulence factor production by two major fungal pathogens of humans, Cryptococcus neoformans, and Candida albicans.

The integrated stress response in budding yeast lifespan extension

Spike D.L. Postnikoff1, Jay E. Johnson2 and Jessica K. Tyler1

 

This article summarizes how the budding yeast Saccharomyces cerevisiae has been instrumental in unraveling the molecular and cellular determinants of aging, and how the induction of cellular stress responses has been associated with experimental lifespan extension, thus underscoring the value of yeast as a model for developing potential aging therapies for humans.

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Inhibitors of glycosomal protein import provide new leads against trypanosomiasis

Vishal C. Kalel1, Leonidas Emmanouilidis2,3, Maciej Dawidowski2,3,4, Wolfgang Schliebs1, Michael Sattler2,3, Grzegorz M. Popowicz2,3, Ralf Erdmann1

This article comments on work published by Dawidowski et al. (Science, 2017), which provides the grounds for further development of the glycosome inhibitors into clinical candidates and validates the parasite protein-protein interactions as drug targets.

Impact of the host on Toxoplasma stage differentiation

Carsten G.K. Lüder1 and Taibur Rahman1

This review summarizes how Toxoplasma gondii transitions from an acute to a chronic infection in warm-blooded animals and humans through a developmental switch influenced by host cell physiology, which determines parasite persistence mainly in neural and muscular tissues.

Chlamydia and mitochondria – an unfragmented relationship

Suvagata Roy Chowdhury1 and Thomas Rudel1

This article comments on work published by Chowdhury et al (J Cell Biol, 2017), which demonstrated that Chlamydia infection induces and requires an upregulation of the host miRNA, miR-30c-5p (miR-30c) to ameliorate infection induced stress on the host mitochondrial architecture and hinders induction of apoptosis.

Integrative modules for efficient genome engineering in yeast

Triana Amen1 and Daniel Kaganovich1

The study introduces a set of vectors with integrative modules designed for effective genome integration into standard marker loci of Saccharomyces cerevisiae, enabling precise expression levels using various promoters and demonstrating the capability of stable multi-gene integration, which is useful for tasks like multi-color cellular imaging and metabolic engineering.

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

Slaven Stekovic1,*, Christoph Ruckenstuhl1,*, Philipp Royer1, Christof Winkler-Hermaden1, Didac Carmona-Gutierrez1, Kai-Uwe Fröhlich1, Guido Kroemer3-8, and Frank Madeo1,2

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.

Protein aggregation triggers a declining libido in elder yeasts that still have a lust for life

Fabrice Caudron

This article comments on work published by Schlissel et al (Science 2017), showing that aging in yeast does not lead to the expected loss of heterochromatin silencing due to Sir2 inactivity, but rather to reduced mating pheromone sensitivity caused by the aggregation of the RNA-binding protein Whi3, which can be reversed by eliminating Whi3's polyglutamine domain.

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The tug-of-war over MTOR in Legionella infections

Stanimir S. Ivanov

This article comments on work published by Abshire et al (PLoS Pathog, 2016), which uncovered that the host metabolic checkpoint kinase Mechanistic target of rapamycin (MTOR) is a central regulator of the pathogen niche expansion program.

A new role for Holliday junction resolvase Yen1 in processing DNA replication intermediates exposes Dna2 as an accessory replicative helicase

Benoît Falquet1,2 and Ulrich Rass

This article comments on work published by Ölmezer et al. (Nat Commun, 2016), which revealed a new function of Yen1, distinct from its previously known role as a Holliday junction resolvase, mediating the removal of branched HR intermediates.

Toxin-mediated gene regulatory mechanism in Staphylococcus aureus

Hwang-Soo Joo and Michael Otto

This article comments on work published by Joo et al. (MBio, 2016), which describes the first molecular regulatory mechanism exerted by an S. aureus toxin, setting a paradigmatic example of how S. aureus toxins may influence cell functions to adjust them to times of toxin production.

Uncovering the hidden: complexity and strategies for diagnosing latent tuberculosis

Mario Alberto Flores-Valdez

This editorial postulates that advanced proteomic and transcriptomic techniques are evolving and may enhance the detection of latent tuberculosis, thereby distinguishing true M. tuberculosis infections from other conditions, which is vital for controlling potential reactivation and transmission.

The Yin & Yang of Mitochondrial Architecture – Interplay of MICOS and F1Fo-ATP synthase in cristae formation

Heike Rampelt1 and Martin van der Laan2

This Editorial posits that mitochondrial cristae architecture is shaped by the interplay of MICOS and ATP synthase, with a recent study illuminating their roles in cristae formation and maintenance.

When a ribosomal protein grows up – the ribosome assembly path of Rps3

Brigitte Pertschy

This article comments on two papers by Mitterer et al., which followed yeast protein Rps3, highlighting the sophisticated mechanisms for protein protection, nuclear transport, and integration into pre-ribosomal particles for final assembly with 40S subunits.

Staphylococcus aureus type I signal peptidase: essential or not essential, that’s the question

Wouter L.W. Hazenbos1, Elizabeth Skippington2 and Man-Wah Tan1

This article comments on work published by Morisaki et al. (mBio, 2016), which characterized a novel ABC transporter. This transporter apparently compensates for SpsB’s essential function by mediating alternative cleavage of a subset of proteins at a site distinct from the SpsB-cleavage site, leading to SpsB-independent secretion.

Transceptors as a functional link of transporters and receptors

George Diallinas

A relative newcomer in environment sensing are the so called transceptors, membrane proteins that possess both solute transport and receptor-like signaling activities. Now, the transceptor concept is further enlarged to include micronutrient sensing via the iron and zinc high-affinity transporters of Saccharomyces cerevisiae.

S. pombe placed on the prion map

Jacqueline Hayles

This article comments on work published by Sideri et al. (Microbial Cell, 2017), which identified the Ctr4 prion in S. pombe.

Using microbes as a key tool to unravel the mechanism of autophagy and the functions of the ATG proteins

Mario Mauthe1,2 and Fulvio Reggiori1,2

Microbes have served to discover and characterize unconventional functions of the ATG proteins, which are uncoupled from their role in autophagy. In our recent study, we have taken advantage of viruses as a screening tool to determine the extent of the unconventional functions of the ATG proteome and characterize one of them.

Post-transcriptional regulation of ribosome biogenesis in yeast

May 1, 2017

Microorganisms adapt to environmental changes by regulating their metabolism, and one key survival strategy is to decrease energy use during adverse conditions by halting ribosome production, with recent findings showing yeast can switch between pre-rRNA processing pathways in response to environmental shifts, adding complexity to ribosome biogenesis regulation.

Placeholder factors in ribosome biogenesis: please, pave my way

April 27, 2017

In ribosome synthesis, "placeholder" factors are crucial trans-acting elements that regulate the timing and assembly of ribosomal proteins, ensuring speed and accuracy in this intricate process by preventing premature interactions and guiding the proper formation of functional ribosomal subunits.

Insights from the redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains

April 25, 2017

This article comments on work published by Li et al. (PloS Pathog, 2017), focusing on Helicobacter pylori infections. They are mostly asymptomatic but can lead to serious conditions, and H. pylori lipopolysaccharide (LPS) is crucial for colonization and persistence, making the study of its structure and biosynthesis pathway vital for understanding pathogenesis and developing treatments.

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.

When a ribosomal protein grows up – the ribosome assembly path of Rps3

March 27, 2017

This article comments on two papers by Mitterer et al., which followed yeast protein Rps3, highlighting the sophisticated mechanisms for protein protection, nuclear transport, and integration into pre-ribosomal particles for final assembly with 40S subunits.

Thiol trapping and metabolic redistribution of sulfur metabolites enable cells to overcome cysteine overload

March 27, 2017

In this study, researchers investigate the mechanisms for handling cysteine overload using Saccharomyces cerevisiae, finding that overexpressing the high affinity cysteine transporter, YCT1, enables yeast cells to rapidly accumulate high levels of intracellular cysteine. The study demonstrates that cells can manage potentially toxic levels of cysteine by converting it to non-reactive thiol forms and utilizing the metabolic products for cell growth.

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.

Evading plant immunity: feedback control of the T3SS in Pseudomonas syringae

March 17, 2017

This article comments on work published by Waite et al. (mBio, 2017), which indicates that a negative autogenous control mechanism, where the sigma factor HrpL represses its own expression, permits the plant pathogen Pseudomonas syringae to fine-tune its type III secretion system, potentially reducing the elicitation of plant immunity and enhancing its ability to cause disease.

Staphylococcus aureus type I signal peptidase: essential or not essential, that’s the question

March 17, 2017

This article comments on work published by Morisaki et al. (mBio, 2016), which characterized a novel ABC transporter. This transporter apparently compensates for SpsB’s essential function by mediating alternative cleavage of a subset of proteins at a site distinct from the SpsB-cleavage site, leading to SpsB-independent secretion.

Microbial flora, probiotics, Bacillus subtilis and the search for a long and healthy human longevity

March 16, 2017

This article comments on work published by Donato et al. (Nat Commun, 2017), which reveals that the probiotic Bacillus subtilis extends the lifespan of Caenorhabditis elegans via mechanisms including the formation of biofilms and the production of signaling molecules like NO and CSF, suggesting a potential pathway through insulin-like signaling that could impact human longevity and age-related diseases.