bims-smemid 2026-08-30 papers

Metabolomics. 2026 Aug 22. pii: 143. [Epub ahead of print]22(5):

Excess glutamine rewires endothelial cell metabolism.

Marzyeh Kheradmand, Xinyao Zhou, Funke Okunrinboye, Ganesh Sriram, Alisa Morss Clyne.

INTRODUCTION: Glutamine, the most abundant amino acid in the body, is a key metabolic substrate for endothelial cells. Glutamine supplementation protects against cardiovascular disease in animal models and in humans; however, glutamine in vitro has inconsistent effects on endothelial function. Furthermore, little is known about how altered metabolite concentrations, for example excess glucose in hyperglycemia or excess glutamine in cell culture media, affect endothelial cell metabolism.
OBJECTIVES: The objective of this study was to determine how physiological and supplemented glutamine affect endothelial metabolism in normal and high glucose conditions.
METHODS: Primary human coronary artery endothelial cells were cultured in varied glutamine concentrations and in normal and high glucose. Glutamine uptake and glutamate secretion were measured using a YSI bioanalyzer; oxidative respiration was assessed using a Seahorse Metabolic Analyzer; and glutamine carbon incorporation into the TCA cycle, amino acids, antioxidants, and other pathways was evaluated via liquid chromatography-mass spectrometry.
RESULTS: As extracellular glutamine increased, endothelial cells took up more glutamine, but glutamate secretion saturated above 2 mM glutamine. Excess glutamine was primarily stored intracellularly, although increasing extracellular glutamine concentration did increase oxidative respiration and TCA cycle isotope enrichment. We also observed increased glutamine incorporation into glutathione, UDP-GlcNAc, and amino acids. When total metabolite abundance was examined, intracellular succinate, unsaturated fatty acids, and one-carbon metabolism-related metabolites decreased with increasing glutamine.
CONCLUSION: These findings demonstrate that excess extracellular glutamine reprograms endothelial metabolism, suggesting that glutamine supplementation should be used with caution in cardiovascular therapies and endothelial cell culture.

DOI: https://doi.org/10.1007/s11306-026-02515-4

Neurobiol Dis. 2026 Aug 28. pii: S0969-9961(26)00333-5. [Epub ahead of print] 107588

Selenoprotein I deficiency disrupts iron homeostasis in brain.

Karlin Wurlitzer, Chi Ma, Lance G A Nunes, Marissa Watanabe, Cole Griffin, Vedbar S Khadka, Antonio G Soares, Fukun W Hoffmann, Peter R Hoffmann, Matthew W Pitts.

Selenoprotein I (SELENOI) is an essential enzyme for phospholipid synthesis that catalyzes the production of plasmenyl-phosphatidylethanolamine (plasmenyl-PE), a key component of myelin that protects and insulates axons. We recently generated a mouse model of central nervous system-restricted SELENOI deficiency that recapitulates features observed in humans with rare loss-of-function SELENOI gene mutations such as motor deficits, diminished plasmenyl-PE, and hypomyelination. Crucially, myelin-producing oligodendrocytes have the highest concentration of iron among cell types in brain. Iron is a vital metal cofactor due to its contribution to redox reactions, but this property also predisposes it to generating reactive oxygen species via Fenton reactions. Moreover, an excess of redox-active iron promotes lipid peroxidation and increases susceptibility to cell death via ferroptosis. In this report, we show that SELENOI deficiency in mouse brain leads to ferroptosis in white matter tracts and promotes iron accumulation. These alterations are accompanied by oligodendrocyte proliferation and elevated numbers of ferritin-positive microglia in affected regions. Overall, our findings detail an intermittent cycle of oligodendrocyte death and proliferation that occurs when SELENOI is absent from the brain, resulting in accelerated iron accrual.

Keywords: Ether lipid; Ferroptosis; Lipid peroxidation; Oligodendrocyte; Selenoprotein; iron

DOI: https://doi.org/10.1016/j.nbd.2026.107588

Int J Mol Med. 2026 Nov;pii: 298. [Epub ahead of print]58(5):

Breaking the cycle of fibrosis: Ferroptosis as a therapeutic target (Review).

Xincheng Feng, Jue Zhang, Qinghong Ma, Chao Sun.

Fibrosis, characterized by abnormal deposition of extracellular matrix, is a chronic disease that progressively remodels tissues, leading to organ failure, earning it the moniker the 'silent killer' of organ function. Recently, ferroptosis, a novel form of regulated cell death, has garnered attention in research; its molecular mechanisms, including the lipid peroxidation cascade, dysregulation of glutathione metabolism and imbalance in iron ion homeostasis, have been closely linked to the progression of fibrosis. The present review systematically elaborates on the process of fibrosis, the main mechanisms of ferroptosis and the role of ferroptosis in fibrosis. The review also discusses intervention strategies targeting the key signaling nodes of ferroptosis during the inflammatory initiation and cell proliferation stages. In addition, it also elaborates on innovative therapeutic strategies based on regulating the ferroptosis pathway, including engineered exosome‑mediated gene delivery systems and iron chelators encapsulated by multifunctional nanoparticles. Through a summary of current evidence, the present review provides a mechanistic rationale and new perspectives for the development of precision anti‑fibrotic therapies targeting ferroptosis.

Keywords: GPX4; ferroptosis; fibrosis; inflammation; lipid peroxidation; proliferation

DOI: https://doi.org/10.3892/ijmm.2026.5969