Vol. 04, 2017

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.

Out with the old: Hsp90 finds amino acid residue more useful than co-chaperone protein

Abbey D. Zuehlke1 and Leonard Neckers1

This article comments on work published by Zuehlke et al (Nat Commun, 2017), which demonstrates that the function of one co-chaperone in yeast is replaced by posttranslational modification (PTM) of a single amino acid within Hsp90 in higher eukaryotes.

Having your cake and eating it – Staphylococcus aureus small colony variants can evolve faster growth rate without losing their antibiotic resistance

Gerrit Brandis1, Sha Cao1, Douglas L. Huseby1 and Diarmaid Hughes1

This article comments on work published by Cao et al. (mBio, 2027), which shows that Staphylococcus aureus can produce small colony variants (SCVs) that are challenging to detect and lead to persistent infections due to mutations affecting respiration and ATP production, with recent findings indicating various evolutionary paths for SCVs to increase growth rate while maintaining antibiotic resistance, suggesting greater adaptability and clinical challenge.

Cristae architecture is determined by an interplay of the MICOS complex and the F1FO ATP synthase via Mic27 and Mic10

Katharina Eydt1,2, Karen M. Davies3, Christina Behrendt4, Ilka Wittig1,5 and Andreas S. Reichert1,2,4,*

This article investigates the roles of MICOS subunits Mic27 and Mic10, revealing their antagonistic and cooperative interactions in crista junction formation and cristae membrane curvature, and proposes a model where F1FO-ATP synthase is connected to MICOS, influencing CJ formation.

Integrative metabolomics as emerging tool to study autophagy regulation

Sarah Stryeck1, Ruth Birner-Gruenberger2, Tobias Madl1,*

This review summarizes the advancements in metabolomics, particularly using NMR spectroscopy and mass spectrometry, and its increasing role in biological research, offering insights into autophagy regulation with a focus on key metabolites, recent studies, and future prospects in elucidating complex regulatory mechanisms of autophagy and related diseases.

The interplay between transcription and mRNA degradation in Saccharomyces cerevisiae

Subhadeep Das1, Debasish Sarkar2 and Biswadip Das1

This review summarizes how the integration of mRNA synthesis and degradation, mediated by specialized promoters and "coordinators," shapes the cellular transcriptome and plays a significant role in regulating gene expression profiles in various biological processes and potentially enhances evolutionary rates.

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.

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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.

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Post-transcriptional regulation of ribosome biogenesis in yeast

Isabelle C. Kos-Braun and Martin Koš

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

Francisco J. Espinar-Marchena, Reyes Babiano1 and Jesús de la Cruz

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

Hong Li1,2, Tiandi Yang3, Tingting Liao2, Aleksandra W. Debowski2,4, Hans-Olof Nilsson2, Stuart M. Haslam3, Anne Dell3, Keith A. Stubbs4, Barry J. Marshall2 and Mohammed Benghezal2,5

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.

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

Christopher Waite1, Jörg Schumacher1, Milija Jovanovic1, Mark Bennett1 and Martin Buck1

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.

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

Facundo Rodriguez Ayala, Carlos Bauman, Sebastián Cogliati, Cecilia Leñini, Marco Bartolini and Roberto Grau

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.

Chlamydia trachomatis’ struggle to keep its host alive

Barbara S. Sixt1-4, Raphael H. Valdivia5, Guido Kroemer1-4,6-7

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

Tâm Mignot1 and Marcelo Nöllmann2

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

Chul-Su Yang

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).

Breaking the bilayer: OMV formation during environmental transitions

Katherine E. Bonnington, Meta J. Kuehn

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.

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.

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.

A new role for the nuclear basket network

November 28, 2017

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

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.

VAMP8 mucin exocytosis attenuates intestinal pathogenesis by Entamoeba histolytica

November 24, 2017

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

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.

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

November 3, 2017

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

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.

Breaking the bad: Bacillus blocks fungal virulence factors

October 30, 2017

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

October 24, 2017

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

October 24, 2017

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.

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