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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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.

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.

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.

Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2

Jinglin L. Xie2,#, Iryna Bohovych3,#, Erin O.Y. Wong2, Jean-Philippe Lambert4, Anne-Claude Gingras2,4, Oleh Khalimonchuk3,5,6, Leah E. Cowen2 and Michelle D. Leach1,2

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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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.

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.

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.

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.

Yeast for virus research

Richard Yuqi Zhao

This article summarizes the use of budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) in virus research, highlighting their advantages for studying viral replication, interaction with host cells, and fundamental cellular processes affected by viruses, while discussing their potential in analyzing small viral genomes and facilitating the discovery of antiviral drugs.

Macrophages as drivers of an opportunistic infection

Annette C. Vergunst1, Nazareth Lopez Carranza1, Lili Zhang1,2, Margarida C. Gomes1, Yara Tasrini1,
Annemarie H. Meijer3 and David O’Callaghan1

This article comments on work published by Mesureur et al. (PloS Pathog, 2017), which shows that macrophages are essential for proliferation of B. cenocepacia in the host. This suggests a new paradigm for Bcc infections and urges the development of novel anti-infectious therapies to efficiently disarm these intrinsically antibiotic resistant facultative intracellular pathogens.

A yeast model for the mechanism of the Epstein-Barr virus immune evasion identifies a new therapeutic target to interfere with the virus stealthiness

María José Lista1, Rodrigo Prado Martins2, Gaelle Angrand1, Alicia Quillévéré1, Chrysoula Daskalogianni2, Cécile Voisset1, Marie-Paule Teulade-Fichou3, Robin Fåhraeus2 and Marc Blondel1

This article comments on a publication by Lista et al. (Nature Communications, 2017) that uncovered the role of the host cell nucleolin (NCL) in EBNA1 self-limitation of expression via a direct interaction of this protein with G-quadruplexes (G4) formed in GAr-encoding sequence of EBNA1 mRNA.

Exacerbating and reversing lysosomal storage diseases: from yeast to humans

Tamayanthi Rajakumar1, Andrew B. Munkacsi1,2 and Stephen L. Sturley3

This article summarizes the use of yeast models in advancing our understanding of lysosomal storage diseases (LSDs), where they have been instrumental in researching LSD mechanisms, screening for therapeutic compounds, and exploring genetic and gene-environment interactions relevant to diseases like Batten disease, cystinosis, and Niemann-Pick type C disease, as well as their connection to broader health issues such as viral infections and obesity.

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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.

Chlamydia trachomatis’ struggle to keep its host alive

March 2, 2017

This article comments on work published by Sixt et al. (Cell Host Microbe, 2016), which analyzed a CpoS-deficient mutant yielding unique insights into the nature of cell-autonomous defense responses against Chlamydia.

New insights into the function of a versatile class of membrane molecular motors from studies of Myxococcus xanthus surface (gliding) motility

March 2, 2017

This article comments on work published by Faure et al. (Nature, 2016), which deciphers force transmission at focal adhesion complexes that are involved in gliding motility in bacteria.

Advancing host-directed therapy for tuberculosis: new therapeutic insights from the Toxoplasma gondii

March 2, 2017

This article comments on work published by Koh et al. (PLoS Pathog, 2017), which uncovered that infection-induced signaling pathways suggest possibilities for the development of novel therapeutic modalities for TB that target the intracellular signaling pathways permitting the replication of Mycobacterium tuberculosis (MTB).

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).

Identification of Ftr1 and Zrt1 as iron and zinc micronutrient transceptors for activation of the PKA pathway in Saccharomyces cerevisiae

March 2, 2017

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.

Transceptors as a functional link of transporters and receptors

March 1, 2017

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

February 3, 2017

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

Balanced CoQ6 biosynthesis is required for lifespan and mitophagy in yeast

February 3, 2017

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.

Breaking the bilayer: OMV formation during environmental transitions

February 3, 2017

This article comments on work published by Bonnington & Kuehn (MBio, 2016), which shows how gram-negative bacteria maintain the barrier properties of the outer membrane (OM) in a wide array of physiological conditions despite their inability to degrade lipopolysaccharide (LPS) and protein material present in the outer leaflet of the OM.

Mutational analysis of fructose-1,6-bis-phosphatase FBP1 indicates partially independent functions in gluconeogenesis and sensitivity to genotoxic stress

February 1, 2017

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.