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Mitochondria in Apoptosis: Bcl-2 Family Members and Mtochondrial Dynamics

Department of Cell Biology, University of Geneva, Faculty of Sciences, 30 quai Ernest-Ansermet, Geneva 4, Switzerland.
Developmental Cell (Impact Factor: 10.37). 07/2011; 21(1):92-101. DOI: 10.1016/j.devcel.2011.06.017
Source: PubMed

ABSTRACT Mitochondria participate in apoptosis through a range of mechanisms that vary between vertebrates and invertebrates. In vertebrates, they release intermembrane space proteins, such as cytochrome c, to promote caspase activation in the cytosol. This process is the result of the loss of integrity of the outer mitochondrial membrane caused by proapoptotic members of the Bcl-2 family. This event is always accompanied by a fissioning of the organelle. Fission of mitochondria has also been reported to participate in apoptosis in Drosophila and Caenorhabditis elegans. However, in these organisms, mitochondrial membrane permeabilization does not occur and the mechanism by which mitochondrial dynamics participates in cell death remains elusive.

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    • "Bax translocation to the mitochondrial membrane creates a pore, which otherwise depolarize the mitochondria membrane potential (Henry-Mowatt et al., 2004). Members of the Bcl-2 family proteins are known to play a critical regulatory role in the apoptosis pathway (Martinou and Youle, 2011). Bcl-2 has been shown to form a heterodimer with Fig. 5. (A) The B103 cells were treated with or without MARE and NAC, and subjected to annexin V/7-AAD staining by FACS. "
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    • "Recent literature suggests that ER-mitochondrial communication regulates multiple aspects of cell biology, including mitochondrial dynamics, which is responsible for maintaining optimal mitochondrial function by balancing the fusion and fission of the mitochondrial network (Hoppins and Nunnari, 2012; Youle and van der Bliek, 2012). Mitochondrial dynamics is regulated by a set of large GTPases that are found in mitochondrial membranes ; the most critical proteins are mitofusins 1 and 2 (Mfn1/ 2) and optic atrophy 1 (OPA1), which cause fusion, and dynamin related protein 1 (DRP1), which promotes fission (Martinou and Youle, 2011). When a cell's mitochondrial network becomes either hyperfused or hyperfragmented, there are metabolic disruptions and collateral negative influences on the mitigation of UPR and cellular fitness. "
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    • "Proteins such as Bcl-2 and Bcl-XL prevent the release of apoptogenic proteins from mitochondria. On the other hand, pro-apoptotic Bcl-2 family members, Bax and Bak, induce outer membrane permeabilization and increased levels of pro-apoptotic factors, such as cytochrome c [8] [17] [20] [37]. "
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