The thioredoxin (TXN) system is an NADPH + H/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This lipid mediator induces TXNRD1 structure changes that modify the FAD interface domain, leading to its activity modulation. The addition of ELV-N34 decreased membrane and cytosolic TXNRD1 activity, suggesting localizations for the targeted reductase. These results show for the first time that the lipid mediator ELV-N34 directly modulates TXNRD1 activity, underling its protection in several pathologies when uncompensated oxidative stress (UOS) evolves.
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http://dx.doi.org/10.1038/s41419-023-06334-6 | DOI Listing |
J Orthop Surg Res
January 2025
Kunshan First People's Hospital Joint Surgery Department, 566 Qianjin East Road, Kunshan City, Suzhou, Jiangsu Province, 215399, China.
Background: Interactions between RNA-binding proteins and RNA regulate RNA transcription during osteoporosis. Ferroptosis, a programmed cell death caused by iron metabolism, plays a vital role in osteoporosis. However, the mechanisms by which RNA-binding proteins are involved in ferroptosis during osteoporosis remain unclear.
View Article and Find Full Text PDFEMBO J
January 2025
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Biogenesis of membrane-bound organelles involves the synthesis, remodeling, and degradation of their constituent phospholipids. How these pathways regulate organelle size remains poorly understood. Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane.
View Article and Find Full Text PDFCurr Obes Rep
January 2025
Department of Endocrinology and Metabolism, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China.
Purpose Of Review: Review the latest data regarding the intersection of adipose tissue (AT) and iron to meet the needs of AT metabolism and the progression of related diseases.
Recent Findings: Iron is involved in fundamental biological metabolic processes and is precisely fine-tuned within the body to maintain cellular, tissue and even systemic iron homeostasis. AT not only serves as an energy storage depot but also represents the largest endocrine organ in the human body, maintaining systemic metabolic homeostasis.
Nat Commun
January 2025
Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with developmental defects, including neural tube defects (NTDs), according to human cohort studies of sporadic and familial cases. The complex mechanisms underlying Vangl-mediated PCP signaling or Vangl-associated human congenital diseases have been hampered by the lack of molecular characterizations of Vangl.
View Article and Find Full Text PDFTrends Biochem Sci
January 2025
Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany; Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Center for Behavioral Brain Sciences, Otto von Guericke University, Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. Electronic address:
The brain is an exceptionally lipid-rich organ with a very complex lipid composition. Lipids are central in several neuronal processes, including membrane formation and fusion, myelin packing, and lipid-mediated signal transmission. Lipid diversity is associated with the evolution of higher cognitive abilities in primates, is affected by neuronal activity, and is instrumental for synaptic plasticity, illustrating that lipids are not static components of synaptic membranes.
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