In the presence of galactose, lithium ions activate the unfolded protein response (UPR) by inhibiting phosphoglucomutase activity and causing the accumulation of galactose-related metabolites, including galactose-1-phosphate. These metabolites also accumulate in humans who have the disease classic galactosemia. Here, we demonstrate that yeast strains harboring a deletion of , a gene encoding a partner of Cdc48p in the endoplasmic reticulum-associated degradation (ERAD) pathway, exhibit delayed UPR activation after lithium and galactose exposure because the deletion decreases galactose-1-phosphate levels. The delay in UPR activation did not occur in yeast strains in which key ERAD or proteasomal pathway genes had been disrupted, indicating that the Δ phenotype is ERAD-independent. We also observed that the Δ strain displays decreased oxygen consumption. The inhibition of mitochondrial respiration was sufficient to diminish galactose-1-phosphate levels and, consequently, affects UPR activation. Finally, we show that the deletion of the AMP-activated protein kinase ortholog-encoding gene can restore the oxygen consumption rate in Δ strain, thereby reestablishing galactose metabolism, UPR activation, and cellular adaption to lithium-galactose challenge. Our results indicate a role for Ubx4p in yeast mitochondrial function and highlight that mitochondrial and endoplasmic reticulum functions are intertwined through galactose metabolism. These findings also shed new light on the mechanisms of lithium action and on the pathophysiology of galactosemia.
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http://dx.doi.org/10.1074/jbc.RA119.011271 | DOI Listing |
Support Care Cancer
December 2024
Physical Therapy Program, Medical Science Campus, University of Puerto Rico, P.O. Box 365967, San Juan, Puerto Rico, 00936-5067, USA.
Purpose: Compare the effects of low-intensity and moderate-intensity exercise on physical functioning in breast cancer survivors.
Methods: Women aged 50 + years and post-primary treatment for stage 0 to III breast cancer were randomly assigned to a 6-month low-intensity (LIG) or moderate-intensity (MIG) exercise group. Participants were instructed to walk (low- or moderate-intensity) for 30 min five days a week, followed by flexibility exercises, and do strengthening and balance exercises twice weekly.
Exp Eye Res
December 2024
Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200031. Electronic address:
We aimed to explore the protective effects and underlying mechanisms of taurine on retinal cells during acute ocular hypertension (AOH)-induced damage. Retinal morphology, apoptosis, mitochondrial structure, electroretinography, expression of GTP binding protein 3 (GTPBP3), and molecules in the unfolded protein response (UPR) were examined in an AOH mouse model and wild-type (WT) mice with or without intravitreal injection of taurine. For in vitro experiments, the GTPBP3 expression and endoplasmic reticulum (ER) stress were examined in R28 cell line under hydrogen peroxide (HO)-induced damage or hypoxia/reoxygenation (H/R)-induced damage, with or without taurine pretreatment.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Faculty of Biology, Moscow State University, Moscow, 119234 Russia.
As a result of molecular domestication of the gag gene of errantiviruses, the Gagr gene was formed in the genome of Drosophila melanogaster. It has previously been shown that the Gagr gene is transcribed at the highest level in gut tissues relative to other tissues, and its transcription is most effectively induced in females in response to ammonium persulfate added to the nutrient medium. In the present work, the gut transcriptome of females with knockdown of the Gagr gene was studied in all tissues under standard conditions and under stress conditions caused by ammonium persulfate.
View Article and Find Full Text PDFOrphanet J Rare Dis
December 2024
Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
Background: the protein phosphatase 3 catalytic subunit alpha (PPP3CA) gene encodes for the alpha isoform of the calcineurin catalytic subunit, which controls the phosphorylation status of many targets. Currently, 23 pathogenic variants of PPP3CA are known, with clinical manifestations varying by mutation type and domain.
Results: through whole exome sequencing, we found two de novo variants in PPP3CA: a frameshift variant predicted leading to a truncated protein in Pt.
Invest Ophthalmol Vis Sci
December 2024
State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Purpose: The purpose of this study was to investigate the potential roles of endoplasmic reticulum (ER) stress in the development of dry eye disease (DED).
Methods: Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, derived from corneal tissues of a dry eye mouse model, was processed using the Seurat R program. The results were validated using a scopolamine-induced dry eye mouse model and a hyperosmotic-induced cell model involving primary human corneal epithelial cells (HCECs) and immortalized human corneal epithelial (HCE-2) cells.
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