CED-9 and EGL-1: A Duo Also Regulating Mitochondrial Network Morphology

Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris cedex 15, France.
Molecular Cell (Impact Factor: 14.02). 04/2006; 21(6):730-2. DOI: 10.1016/j.molcel.2006.03.003
Source: PubMed


In mammalian cells, Bcl-2 family members play a pivotal role in apoptosis by regulating mitochondrial outer membrane permeabilization (MOMP) and subsequent release of apoptogenic factors (Green and Kroemer, 2004). Proapoptotic Bcl-2 family proteins such as Bax trigger cytochrome c release and mitochondrial fragmentation, whereas antiapoptotic proteins (Bcl-2 and Bcl-xL) can inhibit these events (Karbowski and Youle, 2003). In the nematode C. elegans, CED-9, the Bcl-2-related protein, prevents apoptosis by repressing the function of CED-4, a caspase-activating protein. EGL-1, a nematode “BH3-only” protein (a proapoptotic subset of the Bcl-2 family members with only a Bcl-2 homology domain 3) binds to CED-9 and displaces its interaction with CED-4, thereby allowing CED-4 to recruit and activate the caspase CED-3 (Lettre and Hengartner, 2006) (Figure 1). Although CED-9 is anchored to the mitochondria outer membrane, it had not been reported whether CED-9 regulates MOMP and/or mitochondrial morphology during apoptosis.

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    • "In summary, although Bcl-2 family members have been shown to be involved in apoptosis and CED-9 is localized to the mitochondrial membrane, it is not known whether it is associated with MOMP (Estaquier and Arnoult 2006). In the fruit fly Drosophila, the involvement of mitochondria in cell death is less clear and they probably do not undergo MOMP (Varkey et al. 1999), although recent research findings may overturn this notion (see below; Challa et al. 2007; Igaki et al. 2007). "
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    • "This observation raises the possibility that these diseases may be caused by inappropriate and premature cell death. Indeed, recent evidence suggests that the cellular housekeeping role of antiapoptotic Bcl2 family members is to regulate mitochondrial dynamics (Estaquier and Arnoult, 2006). Another possible common cellular defect caused by deficient mitochondrial fusion in humans is the loss of membrane potential and mtDNA, which encodes essential components of respiratory-chain complexes. "
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