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The IRE1α-XBP1s-NFκB axis controls cell survival and epithelial differentiation under osmotic stress through arachidonic acid metabolism activation

Arachidonic acid (AA) metabolism plays a critical role in renal cell osmoadaptation. We recently demonstrated that hypertonicity induces the expression and activation of cytosolic phospholipase A2 (cPLA2). On one hand, AA released by cPLA2 enhances triacylglyceride (TG) synthesis and accumulation. On the other hand, AA is converted into prostaglandins (PG) through cyclooxygenase 2 (COX2) activity. Both processes are required for renal cell survival under osmotic stress. However, the mechanisms by which hypertonicity induces cPLA2 expression remain poorly understood. Given that we previously shown that hypertonicity regulates TG synthesis through the IRE1α-XBP1s branch of the unfolded protein (…)

Burning fat with cysteine depletion

Adams and colleagues comment on two complementary articles by Varghese et al and Lee et al showing that cysteine depletion through combined dietary and genetic means in mice evokes a unique stress response in the liver to amplify these metabolic outcomes and offer a potentially new treatment option for obesity.

Quantifying replication stress in cancer without proliferation confounding

The authors developed a refined gene expression signature (TRSS) that accurately measures replication stress independently of cell proliferation, addressing a major limitation of existing biomarkers that conflate stress with oncogene-driven growth. Applying this signature to patient samples, they discovered that replication stress is associated with activation of the non-homologous end-joining DNA repair pathway, suggesting cells may shift toward this repair mechanism under replication stress conditions.