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Crosstalk with mitochondria occurs at ER–mitochondria contact sites (MAMs), where tightly coupled Ca²⁺ and lipid exchange can propagate ROS signals bidirectionally—ER stress can potentiate mitochondrial ROS production and mitochondrial dysfunction can feed back to intensify ER oxidative pressure—shaping cell-wide redox tone and stress adaptation

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The background to Eduard Buchner’s discovery of cell-free fermentation