title: Phosphate and succinate use different mechanisms to inhibit sugar-induced cell death in yeast: insight into the Crabtree effect.
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 dic1Δ 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Elodie
authors.initials: E
authors.lastname: Burlet
authors.forename: Floyd
authors.initials: F
authors.lastname: Galiano
authors.forename: Magdalena L
authors.initials: ML
authors.lastname: Circu
authors.forename: Tak Yee
authors.initials: TY
authors.lastname: Aw
authors.forename: B Jill
authors.initials: BJ
authors.lastname: Williams
authors.forename: Stephan N
authors.initials: SN
authors.lastname: Witt
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000235:genetics; D005635:Fructosediphosphates / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: D005635:Fructosediphosphates; D010710:Phosphates; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D005947:Glucose; C029063:fructose-1,6-diphosphate