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Mitochondrial reactive oxygen species in cell death signaling
Christophe Fleury1, Bernard Mignotte, Jean-Luc Vayssière
1CNRS-UPRES-A 8087, Laboratoire de génétique moléculaire et physiologique de l'EPHE, université de Versailles/Saint-Quentin, Bâtiment Fermat, 45, avenue des Etats-Unis, 78035 Versailles cedex, France.
Abstract:
During apoptosis, mitochondrial membrane permeability (MMP) increases and the release into the cytosol of pro-apoptotic factors (procaspases, caspase activators and caspase-independent factors such as apoptosis-inducing factor (AIF)) leads to the apoptotic phenotype. Apart from this pivotal role of mitochondria during the execution phase of apoptosis (documented in other reviews of this issue), it appears that reactive oxygen species (ROS) produced by the mitochondria can be involved in cell death. These toxic compounds are normally detoxified by the cells, failing which oxidative stress occurs. However, ROS are not only dangerous molecules for the cell, but they also display a physiological role, as mediators in signal transduction pathways. ROS participate in early and late steps of the regulation of apoptosis, according to different possible molecular mechanisms. In agreement with this role of ROS in apoptosis signaling, inhibition of apoptosis by anti-apoptotic Bcl-2 and Bcl-x(L) is associated with a protection against ROS and/or a shift of the cellular redox potential to a more reduced state. Furthermore, the fact that active forms of cell death in yeast and plants also involve ROS suggests the existence of an ancestral redox-sensitive death signaling pathway that has been independent of caspases and Bcl-2.
Insights
Mitochondria release factors during apoptosis, but also produce reactive oxygen species (ROS) that regulate cell death. ROS are involved in both early and late stages of apoptosis signaling.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Mitochondria play a key role in apoptosis by releasing pro-apoptotic factors.
- Mitochondria also produce reactive oxygen species (ROS), which can contribute to cell death.
- ROS are involved in cellular signaling and can cause oxidative stress when detoxification fails.
Purpose of the Study:
- To explore the role of mitochondrial reactive oxygen species (ROS) in apoptosis.
- To understand the signaling mechanisms involving ROS in cell death.
- To investigate the connection between ROS, apoptosis regulation, and ancestral death pathways.
Main Methods:
- Review of existing literature on apoptosis, mitochondria, and ROS.
- Analysis of molecular mechanisms linking ROS to apoptosis signaling.
- Comparison of ROS involvement in apoptosis across different organisms.
Main Results:
- Mitochondria-derived ROS are implicated in both the execution and signaling phases of apoptosis.
- ROS participate in early and late stages of apoptosis through various molecular pathways.
- Inhibition of apoptosis by Bcl-2 and Bcl-x(L) correlates with protection against ROS.
Conclusions:
- Mitochondria-derived ROS are crucial regulators of apoptosis, acting as signaling molecules.
- ROS-mediated cell death pathways appear to be ancient and independent of caspases and Bcl-2.
- Understanding ROS involvement in apoptosis offers insights into redox-sensitive cell death signaling.