Reference: Lee YJ, et al. (2011) Phosphate and succinate use different mechanisms to inhibit sugar-induced cell death in yeast: insight into the Crabtree effect. J Biol Chem 286(23):20267-74

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Abstract


Stationary-phase Saccharomyces cerevisiae cells transferred from spent rich media into water live for weeks, whereas the same cells die within hours if transferred into water with 2% glucose in a process called sugar-induced cell death (SICD). Our hypothesis is that SICD is due to a dysregulated Crabtree effect, which is the phenomenon whereby glucose transiently inhibits respiration and ATP synthesis. We found that stationary-phase cells in glucose/water consume 21 times more O(2) per cell than exponential-phase cells in rich media, and such excessive O(2) consumption causes reactive oxygen species to accumulate. We also found that inorganic phosphate and succinate protect against SICD but by different mechanisms. Phosphate protects by triggering the synthesis of Fru-1,6-P(2), which inhibits respiration in isolated mitochondria. Succinate protects in wild-type cells but fails to protect in dic1? cells. DIC1 codes for a mitochondrial inner membrane protein that exchanges cytosolic succinate for matrix phosphate. We propose that succinate depletes matrix phosphate, which in turn inhibits respiration and ATP synthesis. In sum, restoring the Crabtree effect, whether with phosphate or succinate, protects cells from SICD.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Lee YJ, Burlet E, Galiano F, Circu ML, Aw TY, Williams BJ, Witt SN
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