Role for CED-9 and Egl-1 as Regulators of Mitochondrial Fission and Fusion Dynamics

• Published in: Molecular cell 2006-03, Vol.21 (6), p.761-773
• Main Authors: Delivani, Petrina, Adrain, Colin, Taylor, Rebecca C., Duriez, Patrick J., Martin, Seamus J.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Apoptosis Regulatory Proteins - physiology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Caenorhabditis elegans Proteins - physiology; Cell Line; CELLCYCLE; Cricetinae; Cytochromes c - metabolism; GTP Phosphohydrolases; Humans; Membrane Proteins - metabolism; Membrane Proteins - physiology; Mitochondria - metabolism; Mitochondria - physiology; Mitochondrial Proteins - metabolism; Mitochondrial Proteins - physiology; PROTEINS; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-bcl-2 - physiology; Repressor Proteins - physiology; Transfection
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2006.01.034

Bcl-2 family proteins play central roles in apoptosis by regulating the release of mitochondrial intermembrane space proteins such as cytochrome c. Death-promoting Bcl-2 family members, such as Bax, can promote cytochrome c release and fragmentation of the mitochondrial network, whereas apoptosis-inhibitory members, such as Bcl-2 and Bcl-xL, can antagonize these events. It remains unclear whether CED-9, the worm Bcl-2 relative, can regulate mitochondrial fission/fusion dynamics or the release of proteins from the mitochondrial intermembrane space. Here, we show that CED-9 interacts with Mitofusin-2/fuzzy onions and can promote mitochondrial clustering and dramatic reorganization of mitochondrial networks. Consistent with its ability to neutralize CED-9 function, EGL-1 antagonized CED-9-dependent remodeling of the mitochondrial network. However, CED-9 failed to inhibit mitochondrial cytochrome c release or apoptosis induced by diverse triggers in mammalian cells. These data suggest that the ability to regulate mitochondrial fission/fusion dynamics is an evolutionarily conserved property of the Bcl-2 family.