title: Metabolic response to MMS-mediated DNA damage in Saccharomyces cerevisiae is dependent on the glucose concentration in the medium.
abstract: Maintenance and adaptation of energy metabolism could play an important role in the cellular ability to respond to DNA damage. A large number of studies suggest that the sensitivity of cells to oxidants and oxidative stress depends on the activity of cellular metabolism and is dependent on the glucose concentration. In fact, yeast cells that utilize fermentative carbon sources and hence rely mainly on glycolysis for energy appear to be more sensitive to oxidative stress. Here we show that treatment of the yeast Saccharomyces cerevisiae growing on a glucose-rich medium with the DNA alkylating agent methyl methanesulphonate (MMS) triggers a rapid inhibition of respiration and enhances reactive oxygen species (ROS) production, which is accompanied by a strong suppression of glycolysis. Further, diminished activity of pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase upon MMS treatment leads to a diversion of glucose carbon to glycerol, trehalose and glycogen accumulation and an increased flux through the pentose-phosphate pathway. Such conditions finally result in a significant decline in the ATP level and energy charge. These effects are dependent on the glucose concentration in the medium. Our results clearly demonstrate that calorie restriction reduces MMS toxicity through increased respiration and reduced ROS accumulation, enhancing the survival and recovery of cells.
authors.affiliation: Institute for Pharmacy and Molecular Biotechnology, Ruperto-Carola University of Heidelberg, Heidelberg, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Kitanovic
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Marie Odile
authors.initials: MO
authors.lastname: Loret
authors.forename: Jinda
authors.initials: J
authors.lastname: Holzwarth
authors.forename: Igor
authors.initials: I
authors.lastname: Kitanovic
authors.forename: Felix
authors.initials: F
authors.lastname: Bonowski
authors.forename: Ngoc
authors.initials: N
authors.lastname: Van Bui
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Francois
authors.forename: Stefan
authors.initials: S
authors.lastname: Wölfl