HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

Review

Reactive oxygen species and the mitochondrial signaling pathway of cell death

M. Le Bras1, M.-V. Clément1, S. Pervaiz1 and C. Brenner1

1CNRS FRE2445, Université de Versailles/St Quentin, LGBC Buffon, Versailles, France, 2Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore and 3Department of Physiology and Oncology Research Institute, Faculty of Medicine, National University of Singapore, Singapore

Offprint requests to: C. Brenner, CNRS FRE 2445, Université de Versailles / St Quentin, LGBC Buffon, 45, avenue des Etats-Unis, 78035 Versailles, France. e-mail: catherinebrenner@yahoo.com


Summary. Reactive oxygen species (ROS) are produced as a by-product of cellular metabolic pathways and function as a critical second messenger in a variety of intracellular signaling pathways. Thus, a defect or deficiency in the anti-oxidant defense system on the one hand and/or the excessive intracellular generation of ROS on the other renders a cell oxidatively stressed. As a consequence, direct or indirect involvement of ROS in numerous diseases has been documented. In most of these cases, the deleterious effect of ROS is a function of activation of intracellular cell-death circuitry. To that end, involvement of ROS at different phases of the apoptotic pathway, such as induction of mitochondrial permeability transition and release of mitochondrial death amplification factors, activation of intracellular caspases and DNA damage, has been clearly established. For instance, the ROS-induced alteration of constitutive mitochondrial proteins, such as the voltage-dependent anion channel (VDAC) and/or the adenine nucleotide translocase (ANT) can induce the pro-apoptotic mitochondrial membrane permabilization. Not only do these observations provide insight into the intricate mechanisms underlying a variety of disease states, but they also present novel opportunities for the design and development of more effective therapeutic strategies. Histol Histopathol 20, 205-220 (2005)

Key words: Apoptosis, Bcl-2, Mitochondria, Reactive oxygen species, Permeability transition pore complex

DOI: 10.14670/HH-20.205