부산대학교 도서관

Copper-depleted cells are more sensitive to cisplatin-induced cytotoxicity due to upregulation of Ctr1, and enhanced accumulation of cis-diamminedichloroplatinum(II) (CDDP). Here we investigated the specific role of mitochondria in enhanced CDDP cytotoxicity under copper-depleted conditions. BY4741 Saccharomyces cerevisiaegrown in yeast peptone and glycerol media were subjected to copper-sufficient or -deficient conditions. These cells were then treated with cisplatin to study the changes in cytochrome coxidase activity, mitochondrial respiration, production of reactive oxygen species, cytosolic pH, translocation of cytochrome cfrom mitochondria to cytosol and mitochondrial membrane potential. Copper deprivation resulted in decreased cytochrome coxidase activity and impaired respiration, which were further augmented by cisplatin. Cisplatin caused the release of mitochondrial cytochrome cand a dramatic drop in the mitochondrial membrane potential (Δ ψm). Also, cisplatin reduced the intracellular cytosolic pH in the copper-deficient cells. Copper-deficiency induced decrease in cytochrome coxidase activity alters mitochondrial respiration which is further worsened by cisplatin, resulting in enhanced apoptosis.