Paracoccidioides brasiliensis is the etiologic agent of one of the most common systemic mycoses in Latin America. As a dimorphic fungus, it must adapt to different environments during its life cycle, either in nature or within the host, enduring external stresses such as temperature or host-induced oxidative stress. In this study we addressed the role of alternative oxidase (PbAOX) in cellular homeostasis during batch culture growth and the morphological transition of P. brasiliensis. Using a PbAOX-antisense-RNA (PbAOX-aRNA) strain with a 70% reduction in gene expression, we show that PbAOX is crucial for maintaining cell viability and vitality during batch culture growth of yeast cells, in what appears to be a pH-dependent manner. We also show that silencing of PbAOX drastically reduced expression levels of other detoxifying enzymes (PbY20 and PbMSOD). In addition, our data indicate that PbAOX plays a role during the morphological transition, namely, during the yeast-to-mycelia germination and mycelia/conidia-to-yeast transition, essential events during the establishment of infection by dimorphic fungal pathogens. Altogether, our findings support the hypothesis that PbAOX is important for the maintenance of cellular homeostasis, possibly by assisting redox balancing during cell growth and the morphological switch of P. brasiliensis.
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http://dx.doi.org/10.1093/mmy/myu091 | DOI Listing |
Sci Adv
January 2025
Division of Molecular Medicine, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Ketogenesis is a dynamic metabolic conduit supporting hepatic fat oxidation particularly when carbohydrates are in short supply. Ketone bodies may be recycled into anabolic substrates, but a physiological role for this process has not been identified. Here, we use mass spectrometry-based C-isotope tracing and shotgun lipidomics to establish a link between hepatic ketogenesis and lipid anabolism.
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January 2025
Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Tissue-specific endothelial cells (ECs) are critical for the homeostasis of pancreatic islets and most other tissues. In vitro recapitulation of islet biology and therapeutic islet transplantation both require adequate vascularization, which remains a challenge. Using human reprogrammed vascular ECs (R-VECs), human islets were functionally vascularized in vitro, demonstrating responsive, dynamic glucose-stimulated insulin secretion and Ca influx.
View Article and Find Full Text PDFJ Cell Biol
April 2025
Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem cell-specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in skin epidermis.
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January 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Contemporary osteoporosis treatment often neglects the intricate interactions among immune cells, signaling proteins, and cytokines within the osteoporotic microenvironment. Here, we developed core-shell nanocapsules composed of a cationized lactoferrin core and an alendronate polymer shell. By tuning the size of these nanocapsules and leveraging the alendronate shell, we enabled precise delivery of small interfering RNA targeting the Semaphorin 4D gene (siSema4D) to specific bone sites.
View Article and Find Full Text PDFAnalyst
January 2025
Jiangxi Provincial Key Laboratory of Organic Functional Molecules; Institute of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
Glutathione (GSH) plays an important role in maintaining redox homeostasis in biological systems. Development of reliable glutathione sensors is of great significance to better understand the role of biomolecules in living cells and organisms. Based on the advantages of the photophysical properties of iridium complexes, we proposed a "turn-on" phosphorescent sensor.
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