Lipid-Mediated Control of ER Function During Apoptosis

Trans-2-hexadecenal (t-2-hex) triggers apoptosis in Saccharomyces cerevisiae by inducing ER stress through Ire1-Hac1 while impairing mitochondrial protein import.

• Why it matters: Lipid-derived metabolites can disrupt organelle homeostasis to regulate cell fate, but how they coordinate ER and mitochondrial dysfunction to promote apoptosis is not fully defined.
• What they did: The authors used yeast to show t-2-hex activates the canonical Ire1-Hac1 unfolded protein response and directly covalently lipidates the ER chaperone Kar2/BiP at a conserved cysteine; they also tested protective roles of Fmp52 and Hfd1 and found Tip30 can substitute for Fmp52.
• The result: Covalent Kar2/BiP modification and proteostasis collapse link lipid exposure to coordinated ER–mitochondrial dysfunction, while Fmp52/Tip30 with Hfd1 counteracts lipid-induced stress and cytotoxicity.

AI summary of the abstract · may contain errors · not medical advice · read the paper.