Research, Research Articles
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.
The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development
Cletus A. Wezena1, Romy Alisch1, Alexandra Golzmann2, Linda Liedgens1, Verena Staudacher1,3, Gabriele Pradel2 and Marcel Deponte1,3
In this study the authors demonstrate that, PfGlo1 and PfcGlo2 are dispensable during asexual blood-stage development while the loss of PfcGlo2 may induce the formation of transmissible gametocytes. These combined data show that PfGlo1 and PfcGlo2 are most likely not suited as targets for selective drug development against the malaria parasite Plasmodium falciparum.
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.
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.
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.
Farnesol inhibits translation to limit growth and filamentation in C. albicans and S. cerevisiae
Nkechi E. Egbe1,2, Tawni O. Dornelles1, Caroline M. Paget1, Lydia M. Castelli1,3 and Mark P. Ashe1
Farnesol, a quorum-sensing molecule, inhibits the switch from yeast to filamentous growth in Candida albicans by impeding translation initiation, differing from fusel alcohols that affect the initiation factor eIF2B, as it disrupts mRNA interaction with the ribosome and prevents preinitiation complex formation.
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.
Predictable regulation of survival by intratumoral microbe-immune crosstalk in patients with lung adenocarcinoma
February 19, 2024
Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.
The last two transmembrane helices in the APC-type FurE transporter act as an intramolecular chaperone essential for concentrative ER-exit
January 5, 2024
FurE is a H+ symporter specific for the cellular uptake of uric acid, allantoin, uracil, and toxic nucleobase analogues in the fungus Aspergillus nidulans. Being member of the NCS1 protein family, FurE is structurally related to the APC-superfamily of transporters.
Basal level of ppGpp coordinates Escherichia coli cell heterogeneity and ampicillin resistance and persistence
October 25, 2023
The universal stringent response alarmone ppGpp (guanosine penta and tetra phosphates) plays a crucial role in various aspects of fundamental cell physiology (e.g., cell growth rate, cell size) and thus bacterial tolerance to and survival of external stresses, including antibiotics. In tihs study, we discuss the fundamental role of basal level of ppGpp in regulating cell homogeneity and ampicillin persistence.
Investigation of the acetic acid stress response in Saccharomyces cerevisiae with mutated H3 residues
August 18, 2023
Yeast cells respond to acetic acid in diverse ways. Here, we have elucidated the deleterious effects of acetic acid on different histone mutants
The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella
August 17, 2023
Here we investigated why 5,6-dimethylbenzimidazole (DMB) inhibits in S. Typhimurium. Briefly, we determined that the structural similarities of the substituted benzene ring of DMB with the isoalloxazine moiety of flavins is responsible for the deleterious effects of this CoB12 precursor.
Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2
August 8, 2023
We show here that apart from its effector role for Elongator-dependent tRNA modification in yeast, Kti13 alias Dph8 also operates in step one of the diphthamide modification pathway.