Kuznetsov 2011 Biochim Biophys Acta

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Kuznetsov AV, Margreiter R, Amberger A, Saks V, Grimm M (2011) Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death. Biochim Biophys Acta 1813:1144-52.

» PMID:21406203

Kuznetsov AV, Margreiter R, Amberger A, Saks V, Grimm M (2011) Biochim Biophys Acta

Abstract: Mitochondria play central roles in cell life as a source of energy and in cell death by inducing apoptosis. Many important functions of mitochondria change in cancer, and these organelles can be a target of chemotherapy. The widely used anticancer drug doxorubicin (DOX) causes cell death, inhibition of cell cycle/proliferation and mitochondrial impairment. However, the mechanism of such impairment is not completely understood. In our study we used confocal and two-photon fluorescence imaging together with enzymatic and respirometric analysis to study short- and long-term effects of doxorubicin on mitochondria in various human carcinoma cells. We show that short-term (<30 min) effects include i) rapid changes in mitochondrial redox potentials towards a more oxidized state (flavoproteins and NADH), ii) mitochondrial depolarization, iii) elevated matrix calcium levels, and iv) mitochondrial ROS production, demonstrating a complex pattern of mitochondrial alterations. Significant inhibition of mitochondrial endogenous and uncoupled respiration, ATP depletion and changes in the activities of marker enzymes were observed after 48 h of DOX treatment (long-term effects) associated with cell cycle arrest and death. Keywords: confocal imaging, doxorubicin, mitochondria, mitochondrial function, redox state, reactive oxygen species (ROS)

O2k-Network Lab: FR_Grenoble_Saks VA


Stress:Cell death, Oxidative stress;RONS  Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Intact cells 

HRR: Oxygraph-2k 

colon cancer, breast cancer