Cisplatin mediated impairment of mitochondrial DNA metabolism inversely correlates with glutathione levels

Nuria Garrido , Acisclo Pérez-Martos , Mercedes Faro , José Manuel Lou-Bonafonte , Patricio Fernández-Silva , Manuel José López-Pérez , Julio Montoya , José A Enríquez (1)

1 Dpto. Bioquimica y Biología Molecular y Celular

Cisplatin accumulates in mitochondria being this organelle a major target for this drug in cancer cells. Thus, alterations in mitochondrial function have been implicated in cancer cell resistance to chemotherapeutic agents. Moreover, cisplatin toxic side effects seem to be associated with mitochondrial injury in vivo and in vitro. In order to clarify the potential effect of cisplatin in mitochondrial DNA maintenance and expression, we have analyzed rat liver mitochondrial DNA and RNA synthesis as well as their stability under the influence of in vivo treatment or in vitro exposure to cisplatin. We show that cisplatin causes a direct and significant impairment of mtDNA and mtRNA synthesis and decreased steady state levels of mtRNAs in isolated mitochondria. Furthermore, in vivo treatment of the animals with cisplatin exerted a protective effect from the impairment on mitochondrial RNA metabolism caused by in vitro exposure to the drug, by means of increased mitochondrial GSH levels after in vivo cisplatin treatment.

Mots clés: Life Sciences

Nuria Garrido, Acisclo Pérez-Martos, Mercedes Faro, José Manuel Lou-Bonafonte, Patricio Fernández-Silva, et al.. Cisplatin mediated impairment of mitochondrial DNA metabolism inversely correlates with glutathione levels. Biochemical Journal, 2008, 414 (1), pp.93-102. ⟨10.1042/BJ20071615⟩. ⟨hal-00478928⟩