Research, Research Articles
The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription
Rubin Jiao1, Liubov Lobanova1, Amanda Waldner1, Anthony Fu1, Linda Xiao1, Troy A. Harkness1, and Terra G. Arnason1,2
The SNF1 kinase class of serine/threonine kinases, which includes the AMP-dependent protein kinase (AMPK) in other systems, are of widespread interest because of their important roles in glucose homeostasis, stress resistance, and aging. Our goal was to identify discrete ubiquitin-conjugating enzymes that are involved in SNF1 kinase activity in response to glucose levels and anticipated revealing those which are involved in Snf1-Ub attachment. Here, we report that the cell cycle and stress-related E2, Ubc1, indirectly affects SNF1 kinase activity not through stability, but through upstream events.
Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets
January Weiner 3rd1 and Taco W.A. Kooij2
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites.
VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast
Dário Trindade1,2, Clara Pereira3,4, Susana R. Chaves1, Stéphen Manon2, Manuela Côrte-Real1 and Maria João Sousa1
Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. In this study, we sought to determine whether Por1p functionally interacts with ADP/ATP carrier (AAC) proteins, as well as its contribution to cytochrome c release and yeast apoptosis induced by acetic acid treatment. Our data indicate that Por1p may regulate cell survival by acting as a negative regulator of AAC proteins in the apoptotic cascade.
Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging
Andrea L. Ruetenik1,2,3, Alejandro Ocampo1,2,3,¶, Kai Ruan4,5,#, Yi Zhu4,5, Chong Li4,6, R. Grace Zhai1,4,5,6 and Antoni Barrientos1,2,3,5
Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We could shown that enhancement of mitochondrial biogenesis protects against neurodegeneration in HD yeast and fly models. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.
Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis
Richard Dela Cruz1,2, Mi-Young Jeong1 and Dennis R. Winge1
Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. In this report, we describe the isolation of a robust suppressor of the respiratory defect in cox23∆ cells that mapped to the mitochondrial-encoded Cox1 subunit.
Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon
Anastasiya Epshtein1, Catherine J. Potenski2, and Hannah L. Klein1
Ribonucleotides (rNMPs) can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. We report here that recombination is not stimulated by rNMPs incorporated by the replicative polymerase epsilon. Instead, recombination seems to be stimulated by multiple contiguous rNMPs, which may arise from R-loops or replication priming events.
Construction and evaluation of yeast expression networks by database-guided predictions
Katharina Papsdorf1,#, Siyuan Sima1,#, Gerhard Richter2, Klaus Richter1
DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We set out to define a way to cluster microarray data according to their expressional relationship and to obtain information on the significance of this clustering approach.
Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii
Arunakar Kuchipudi1, Ruben D. Arroyo-Olarte1, Friederike Hoffmann1, Volker Brinkmann2, Nishith Gupta1, 2
Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Using an optogenetic sensor to monitor subcellular calcium in this model intracellular pathogen we found a novel regulatory function of phosphatidylthreonine in calcium signaling.
Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1
David J. Laprade, Melissa S. Brown#, Morgan L. McCarthy#, James J. Ritch, and Nicanor Austriaco
Candida albicans proliferates in two distinct cell types: blastopores and filaments. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We provide evidence that programmed cell death is cell-type specific in yeast: Filamentous C. albicans cells are more resistant to amphotericin B- and caspofungin-induced programmed cell death than their blastospore counterparts. Our genetic data suggest that this phenomenon is mediated by a protective mechanism involving the yeast metacaspase, MCA1.
Measurement of apoptosis by SCAN©, a system for counting and analysis of fluorescently labelled nuclei
November 26, 2014
This work reports on a system for analyses of apoptosis-like programmed cell death in fungal hyphae that is composed of several modules, which enable automatic quantification of nuclei with chromatin condensation and DNA strand break in large datasets according to nuclei-associated fluorescent markers.
Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan
November 18, 2014
This work shows that MPC1-deficient cells make up for their impairment in mitochondrial pyruvate with a metabolic rewiring which involves several intermediates of the mitochondrially localized TCA cycle and the cytosolic glyoxylate shunt but ultimately results in a pro-aging process.
Overexpression of the transcription factor Yap1 modifies intracellular redox conditions and enhances recombinant protein secretion
October 31, 2014
This article investigates the role of Yap1 during the production of recombinant secretory proteins in glucose based growth conditions in Pichia pastoris, and reports a novel role of Yap1 during ER-resident oxidative protein folding.
Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature
October 29, 2014
This study confirms the importance of specific genes in growth and fermentation activity of Saccharomyces cerevisiae at low temperature.
Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin
October 24, 2014
This study reports the identification of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) and shows that specific ARBs increase yeast tolerance to Cu and Cp, and affect markers of Cu-induced apoptosis. Likewise, this study finds that specific ARBs increase human cell line tolerance to Cu and decrease the prevalence of apoptotic markers.
An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids
October 1, 2014
This work describes a novel family of type I membrane proteins ("invariant glycoproteins") and proposes them as trypanosomatid-specific ER-localised glycoproteins, with potential contributions to life cycle progression and immunity, that utilise oligomerisation as an ER retention mechanism.
Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program
September 1, 2014
Using multiple approaches, this work implies a nucleosome focusing event as a key step that resets transcription during the respiratory oscillation.
Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae
August 27, 2014
This work characterizes the involvement of MAPK signaling pathways in cell death induced by acetic acid in Saccharomyces cerevisiae.
Extracellular calcium triggers unique transcriptional programs and modulates staurosporine-induced cell death in Neurospora crassa
August 9, 2014
The results presented here reveal that in Neurospora crassa, extracellular Ca2+ modulates cell death and the transcriptional alterations induced by staurosporine, and lead to the identification of two novel putative Ca2+-binding proteins, encoded by the NCU08524 and NCU06607 genes.
Multiple metabolic requirements for size homeostasis and initiation of division in Saccharomyces cerevisiae
August 1, 2014
This article reveals an unexpected diversity in the G1 cell cycle phenotypes of metabolic and biosynthetic Saccharomyces cerevisiae mutants, suggesting that growth requirements for cell division are multiple, distinct and imposed throughout the G1 phase of the cell cycle.