Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death.

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.
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BBA - Biochimica et Biophysica Acta, Elsevier, 2011, 1813 (6), pp.1144-52. 〈10.1016/j.bbamcr.2011.03.002〉
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Soumis le : lundi 17 octobre 2011 - 14:48:34
Dernière modification le : mardi 23 janvier 2018 - 10:56:32

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Andrey Kuznetsov, Raimund Margreiter, Albert Amberger, Valdur Saks, Michael Grimm. Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death.. BBA - Biochimica et Biophysica Acta, Elsevier, 2011, 1813 (6), pp.1144-52. 〈10.1016/j.bbamcr.2011.03.002〉. 〈inserm-00633082〉

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