title: Cisplatin cytotoxicity is dependent on mitochondrial respiration inSaccharomyces cerevisiae.
abstract: OBJECTIVE
  To understand the role of mitochondrial respiration in cisplatin sensitivity, we have employed wild-type and mitochondrial DNA depleted Rho0 yeast cells.
  
  
  METHODS
  Wild type and Rho0 yeast cultured in fermentable and non-fermentable sugar containing media, were studied for their sensitivity against cisplatin by monitoring growth curves, oxygen consumption, pH changes in cytosol/mitochondrial compartments, reactive oxygen species production and respiratory control ratio.
  
  
  RESULTS
  Wild-type yeast grown on glycerol exhibited heightened sensitivity to cisplatin than yeast grown on glucose. Cisplatin (100 μM), although significantly reduced the growth of wild- type cells, only slightly altered the growth rate of Rho0 cells. Cisplatin treatment decreased both pHcytand pHmitto a similar extent without affecting the pH difference. Cisplatin dose-dependently increased the oxidative stress in wild-type, but not in respiration-deficient Rho0 strain. Cisplatin decreased the respiratory control ratio.
  
  
  CONCLUSIONS
  These results suggest that cisplatin toxicity is influenced by the respiratory capacity of the cells and the intracellular oxidative burden. Although cisplatinper seslightly decreased the respiration of yeast cells grown in glucose, it did not disturb the mitochondrial chemiosmotic gradient.
authors.affiliation: Institute of Genetics & Hospital for Genetic Diseases, Osmania University, Hyderabad, Telangana, India-500016.
authors.forename: Santhi Priya
authors.initials: SP
authors.lastname: Inapurapu
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad, Telangana, India- 500007.
authors.forename: Karunakar Rao
authors.initials: KR
authors.lastname: Kudle
authors.affiliation: Department of Biochemistry, Kakatiya University, Warangal, Telangana, India -506009.
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Bodiga
authors.affiliation: Institute of Genetics & Hospital for Genetic Diseases, Osmania University, Hyderabad, Telangana, India-500016.
authors.forename: Vijaya Lakshmi
authors.initials: VL
authors.lastname: Bodiga
keywords: Cisplatin; Mitochondria; Oxidative phosphorylation; Respiration; Rho0