Vol. 02, 2015
Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome
R. Roshini Beenukumar1,#, Daniela Gödderz1,2,#, R. Palanimurugan1,3, and R. Jürgen Dohmen1
Ornithine decarboxylase (ODC), a ubiquitin-independent substrate of the proteasome, is a homodimeric protein with a rate-limiting function in polyamine biosynthesis. Polyamines regulate ODC levels by a feedback mechanism mediated by ODC antizyme (OAZ). Higher cellular polyamine levels trigger the synthesis of OAZ and also inhibit its ubiquitin-dependent proteasomal degradation. OAZ binds ODC monomers and targets them to the proteasome. Here, we report that polyamines, aside from their role in the control of OAZ synthesis and stability, directly enhance OAZ-mediated ODC degradation by the proteasome. Using a stable mutant of OAZ, we show that polyamines promote ODC degradation in Saccharomyces cerevisiae cells even when OAZ levels are not changed. Furthermore, polyamines stimulated the in vitro degradation of ODC by the...
Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly
Kristin Graumann1,3,#, Frieder Schaumburg1,4,#, Thomas F. Reubold2, Diana Hippe1, Susanne Eschenburg2 and Carsten G. K. Lüder1
Inhibition of programmed cell death pathways of mammalian cells often facilitates the sustained survival of intracellular microorganisms. The apicomplexan parasite Toxoplasma gondii is a master regulator of host cell apoptotic pathways. Here, we have characterized a novel anti-apoptotic activity of T. gondii. Using a cell-free cytosolic extract model, we show that T. gondii interferes with the activities of caspase 9 and caspase 3/7 which have been induced by exogenous cytochrome c and dATP. Proteolytic cleavage of caspases 9 and 3 is also diminished suggesting inhibition of holo-apoptosome function. Parasite infection of Jurkat T cells and subsequent triggering of apoptosome formation by exogenous cytochrome c in vitro and in vivo indicated that...
Understanding grapevine-microbiome interactions: implications for viticulture industry
Iratxe Zarraonaindia1,2 and Jack A. Gilbert3,4,5,6
This microreview discusses the article "The soil microbiome influences grapevine-associated microbiota" by Zarraonaindia et al. (2015), MBio, which reports that the grapevine-associated microbiota depends on the soil microbiome.
Cytokinins beyond plants: synthesis by Mycobacterium tuberculosis
Marie I. Samanovic and K. Heran Darwin
This microreview discusses "Proteasomal Control of Cytokinin Synthesis Protects Mycobacterium tuberculosis against Nitric Oxide" by Samanovic et al. (2015), Mol Cell.
Exogenous folates stimulate growth and budding of Candida glabrata
Afsaneh Porzoor and Ian G. Macreadie
Folate, vitamin B9, is well recognized as being essential for cell growth. The utilization of folate is common to all cells, but the source of it may be quite different. This article reports a novel response of yeast to folates that may increase the utility of yeast as a model to study folate transport and signaling.
Yeast as a model system to study metabolic impact of selenium compounds
Enrique Herrero1,* and Ralf Erik Wellinger2
Inorganic Se forms such as selenate or selenite (the two more abundant forms in nature) can be toxic in Saccharomyces cerevisiae cells, which constitute an adequate model to study such toxicity at the molecular level and the functions participating in protection against Se compounds. In this article, the authors propose that yeast may be used to improve our knowledge on the impact of Se on metal homeostasis, the identification of Se-targets at the DNA and protein levels, and to gain more insights into the mechanism of Se-mediated apoptosis.
Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
Camilla Ceccatelli Berti1, Cristina Dallabona1, Mirca Lazzaretti1, Sabrina Dusi2, Elena Tosi1, Valeria Tiranti2, Paola Goffrini1
Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. Yeast expressing a pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.
Understanding structure, function, and mutations in the mitochondrial ATP synthase
Ting Xu1, Vijayakanth Pagadala2, David M. Mueller1
This review summarizes the current understanding of the subunit composition of the ATP synthase and the role of the subunits followed by a discussion on known mutations and their effect on the activity of the ATP synthase. The concludes with a summary of mutations in genes encoding subunits of the ATP synthase that are known to be responsible for human disease, and a brief discussion on SNPs.
Modeling non-hereditary mechanisms of Alzheimer disease during apoptosis in yeast
Ralf J. Braun1,#, Cornelia Sommer2,3,#, Christine Leibiger1,#, Romina J.G. Gentier4,#, Verónica I. Dumit5, Katrin Paduch1, Tobias Eisenberg2, Lukas Habernig2, Gert Trausinger6, Christoph Magnes6, Thomas Pieber6,7, Frank Sinner6,7, Jörn Dengjel5, Fred W. van Leeuwen4, Guido Kroemer8-11, and Frank Madeo2,3
Impaired protein degradation and mitochondrial dysfunction are believed to contribute to neurodegenerative disorders, including Alzheimer disease (AD). This microreview comments on the article "Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin" by Braun et al. (2015), Cell Rep.
Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
Camilla Ceccatelli Berti1, Cristina Dallabona1, Mirca Lazzaretti1, Sabrina Dusi2, Elena Tosi1, Valeria Tiranti2, Paola Goffrini1
Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. Yeast expressing a pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.
Understanding structure, function, and mutations in the mitochondrial ATP synthase
Ting Xu1, Vijayakanth Pagadala2, David M. Mueller1
This review summarizes the current understanding of the subunit composition of the ATP synthase and the role of the subunits followed by a discussion on known mutations and their effect on the activity of the ATP synthase. The concludes with a summary of mutations in genes encoding subunits of the ATP synthase that are known to be responsible for human disease, and a brief discussion on SNPs.
Modeling non-hereditary mechanisms of Alzheimer disease during apoptosis in yeast
Ralf J. Braun1,#, Cornelia Sommer2,3,#, Christine Leibiger1,#, Romina J.G. Gentier4,#, Verónica I. Dumit5, Katrin Paduch1, Tobias Eisenberg2, Lukas Habernig2, Gert Trausinger6, Christoph Magnes6, Thomas Pieber6,7, Frank Sinner6,7, Jörn Dengjel5, Fred W. van Leeuwen4, Guido Kroemer8-11, and Frank Madeo2,3
Impaired protein degradation and mitochondrial dysfunction are believed to contribute to neurodegenerative disorders, including Alzheimer disease (AD). This microreview comments on the article "Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin" by Braun et al. (2015), Cell Rep.
Translate to divide: сontrol of the cell cycle by protein synthesis
Michael Polymenis1 and Rodolfo Aramayo2
Protein synthesis underpins much of cell growth and, consequently, cell multiplication. Understanding how proliferating cells commit and progress into the cell cycle requires knowing not only which proteins need to be synthesized, but also what determines their rate of synthesis during cell division. Experiments with proliferating populations of microbial strains, animal or plant cell lines, have rigorous expectations. Under the same culture conditions, cells ought to have the same properties and composition in every single experiment. The basic “metrics” of proliferating cells remain constant, even after many rounds of cell division. These metrics include cellular mass and volume, and macromolecular composition. The constancy of such parameters reflects the fundamental ability of cells to coordinate their growth with their division. Balancing cell growth with cell division determines the overall rates of cell proliferation...
New roles for autophagy and spermidine in T cells
D. J. Puleston and A. K. Simon
This microreview discusses the article "Autophagy is a critical regulator of memory CD8+ T cell formation" by Puleston et al. (2014), eLife.
Characterization of the Maf family of polymorphic toxins in pathogenic Neisseria species
Anne Jamet1,2,3,4,5, Xavier Nassif2,3,4,5
In addition to harmless commensal species, Neisseria genus encompasses two pathogenic species, N. meningitidis (the meningococcus) and N. gonorrhoeae (the gonococcus), which are responsible for meningitis and genital tract infections, respectively. This microreview comments on the article "A new family of secreted toxins in pathogenic Neisseria species" by Jamet et al. (2015), PLoS Pathog.
Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi
Alberto Elías-Villalobos1,2, Dominique Helmlinger2 and José I. Ibeas1
Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Elías-Villalobos et al. propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.
Electron microscopy for ultrastructural analysis and protein localization in Saccharomyces cerevisiae
Andri Frankl, Muriel Mari and Fulvio Reggiori
The yeast Saccharomyces cerevisiae is a key model system for studying of a multitude of cellular processes because of its amenability to genetics, molecular biology and biochemical procedures. The goal of this review is to guide researchers that want to investigate a particular process at the ultrastructural level in yeast by aiding in the selection of the most appropriate approach to visualize a specific structure or subcellular compartment.
A bacterial volatile signal for biofilm formation
Yun Chen2, Kevin Gozzi1, and Yunrong Chai1
Bacteria constantly monitor the environment they reside in and respond to potential changes in the environment through a variety of signal sensing and transduction mechanisms in a timely fashion. In their recent study (Chen, et al. mBio (2015), 6: e00392-15), the authors demonstrated that the soil bacterium Bacillus subtilis uses acetic acid as a volatile signal to coordinate the timing of biofilm formation within physically separated cells in the community. They also showed that the bacterium possesses an intertwined gene network to produce, secrete, sense, and respond to acetic acid, in stimulating biofilm formation.
The great escape: Pseudomonas breaks out of the lung
Angelica Zhang1, Stephanie M. Rangel1, and Alan R. Hauser1,2
The Gram-negative bacterium Pseudomonas aeruginosa is a major cause of hospital-acquired infections and the focus of much attention due to its resistance to many conventional antibiotics. This article discusses the potential mechanisms by which these processes occur as well as the novel techniques used to study ExoS function in vivo.
Peering into the ‘black box’ of pathogen recognition by cellular autophagy systems
Shu-chin Lai# and Rodney J Devenish
Autophagy is an intracellular process that plays an important role in protecting eukaryotic cells and maintaining intracellular homeostasis. This review summarises the available evidence regarding the specific recognition of invading pathogens by which they are targeted into host autophagy pathways.
Per aspera ad astra: When harmful chromosomal translocations become a plus value in genetic evolution. Lessons from Saccharomyces cerevisiae
Valentina Tosato and Carlo V. Bruschi
This review will focus on chromosomal translocations (either spontaneous or induced) in budding yeast. Indeed, very few organisms tolerate so well aneuploidy like Saccharomyces, allowing in depth studies on chromosomal numerical aberrations. The phenomenon of post-translocational adaptation (PTA) is discussed, providing some new unpublished data and proposing the hypothesis that translocations may drive evolution through adaptive genetic selection.
Intracellular phase for an extracellular bacterial pathogen: MgtC shows the way
Audrey Bernut1,#, Claudine Belon1, Chantal Soscia2, Sophie Bleves2, Anne-Béatrice Blanc-Potard1
This article discusses the article "A macrophage subversion factor is shared by intracellular and extracellular pathogens" by Belon et al. (PLoS Pathogens 11(6): e1004969, 2015).
The role of transcriptional ‘futile cycles’ in autophagy and microbial pathogenesis
Guowu Hu1, Travis McQuiston1, Amélie Bernard2, Yoon-Dong Park1, Jin Qiu1, Ali Vural3, Nannan Zhang1, Scott R. Waterman1, Nathan H. Blewett4, Timothy G. Myers5, John H. Kehrl3, Gulbu Uzel1, Daniel J. Klionsky2 and Peter R. Williamson1
Eukaryotic cells utilize macroautophagy (hereafter autophagy) to recycle cellular materials during nutrient stress. Target of rapamycin (Tor) is a central regulator of this process, acting by post-translational mechanisms, phosphorylating preformed autophagy-related (Atg) proteins to repress autophagy during log-phase growth. A role for this regulatory process in fungal virulence was further demonstrated by showing that overexpression of the Dcp2-associated mRNA-binding protein Vad1 in the AIDS-associated pathogen Cryptococcus neoformans results in constitutive repression of autophagy even under starvation conditions as well as attenuated virulence in a mouse model. In summary, Tor-dependent post-transcriptional regulation of autophagy plays a key role in the facilitation of microbial pathogenesis.
The many facets of homologous recombination at telomeres
Clémence Claussin and Michael Chang
The ends of linear chromosomes are capped by nucleoprotein structures called telomeres. A dysfunctional telomere may resemble a DNA double-strand break (DSB), which is a severe form of DNA damage. The presence of one DSB is sufficient to drive cell cycle arrest and cell death. Therefore cells have evolved mechanisms to repair DSBs such as homologous recombination (HR). HR-mediated repair of telomeres can lead to genome instability, a hallmark of cancer cells, which is why such repair is normally inhibited. However, some HR-mediated processes are required for proper telomere function. The need for some recombination activities at telomeres but not others necessitates careful and complex regulation, defects in which can lead to catastrophic consequences. Furthermore, some cell types can maintain telomeres via telomerase-independent, recombination-mediated mechanisms. In humans, these mechanisms...
Quorum protection, growth and survival
Ian G . Macreadie
For the growth of a cell culture, one inoculates not with one cell but with a quorum of cells. This most often a requirement, not just a convenience, and most of us take this for granted without question. Here this observation is re-examined to understand why a quorum may be required to grow cells. The importance of quorums may be widespread in the aspects of microbiology they affect. It is very likely that quorums are connected with and have a large impact on the determination of Minimal Inhibitory Concentrations. It is also possible that low cell density may adversely affect cell survival, however, this is an area where even less is known. The need for a quorum might affect other aspects of microbial cell culture, cell isolation and cell preservation. Effects also extend to mammalian cell culture. Here I seek to review studies that have been documented and speculate on how the information might be utilized in the future.
The emerging role of complex modifications of tRNALysUUU in signaling pathways
Patrick C. Thiaville1,2,3,4 and Valérie de Crécy-Lagard2,4
This comment discusses the article "Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling" by Scheidt et al (Microbial Cell, 2014).
Targeting of chromatin readers: a novel strategy used by the Shigella flexneri virulence effector OspF to reprogram transcription
December 28, 2014
In this microreview, the authors discuss the article "Shigella flexneri targets the HP1γ subcode through the phosphothreoninelyase OspF" by Harouz et al. (2014), EMBO J, 22 : 2606-2622.