Research, Research Articles
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.
Formaldehyde fixation is detrimental to actin cables in glucose-depleted S. cerevisiae cells
Pavla Vasicova1,#, Mark Rinnerthaler2, Danusa Haskova1, Lenka Novakova1, Ivana Malcova1, Michael Breitenbach2, Jiri Hasek1
Actin filaments form cortical patches and emanating cables in fermenting cells of Saccharomyces cerevisiae. We assume that stability of actin cables reflects the metabolic status of the cell. Based on comparison of live and formaldehyde-fixed cells, our data suggest that formaldehyde affects respiration before fixation and this uneven signaling results in destabilization of actin cables in glucose-deprived cells.
Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids
March 12, 2020
This study identifies (-)-drimenol as a potent broad-spectrum antifungal agent effective against multiple pathogenic fungi, including drug-resistant strains, and reveals its mechanism of action involves disruption of fungal membranes and targeting Crk1-related pathways, with potential for structural optimization to enhance efficacy.
Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae
February 5, 2020
This study introduces GFP-based transcriptional reporters driven by a calcineurin-dependent response element, enabling real-time monitoring of calcineurin activity in live yeast cells for studying stress responses, aging, and antifungal drug screening.
The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast
January 3, 2020
This study reveals that the loss of heterochromatin silencing in Set2-deficient cells is due to unrestrained Mst2C activity, highlighting the need for spatially restricted chromatin-modifying enzymes to maintain distinct chromatin states.
Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection
December 3, 2019
This study reveals that the plasma membrane SNARE proteins SNAP-23 and Syntaxin 4 are crucial for Chlamydia trachomatis development by regulating lipid droplet homeostasis and supporting the formation of infectious progeny within host cells.
Yeast can express and assemble bacterial secretins in the mitochondrial outer membrane
November 19, 2019
Secretins, essential components of bacterial secretion systems, can be expressed in yeast and show differential dependencies on mitochondrial import and assembly factors for membrane integration, suggesting diverse pathways for their assembly into the bacterial outer membrane.
Metabolic reprogramming of Salmonella infected macrophages and its modulation by iron availability and the mTOR pathway
November 14, 2019
This article shows that iron plays a critical role in both the immune response and metabolic reprogramming of macrophages during infection, influencing the TCA cycle and mTOR pathway, with implications for the growth of intracellular bacteria like Salmonella.
Transcriptomic and chemogenomic analyses unveil the essential role of Com2-regulon in response and tolerance of Saccharomyces cerevisiae to stress induced by sulfur dioxide
September 30, 2019
This article shows that in the presence of sulfur dioxide (SO2), the transcription factor Com2 plays a critical role in the tolerance and response of Saccharomyces cerevisiae, affecting the expression of a majority of SO2-activated genes and contributing to the protection against stress induced by SO2 at an enologically relevant pH.
Network dynamics of the yeast methyltransferome
July 9, 2019
This article presents a systematic genetic analysis of methyltransferases (MTases) under normal and stress conditions, uncovering the complex and adaptive nature of the methyltransferome and discovering a potential connection between phospholipid methylation and histone methylation, suggesting interplay between lipid homeostasis and epigenetic regulation.
Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase
May 20, 2019
This article shows that the carbon source affects the abundance of ribonucleotide reductase (RNR) subunits in yeast, with a novel Mec1 signaling axis regulating Rnr3 independently of known DNA damage response pathways, and reveals Rnr3's unexpected role in mitochondrial function.