Role for CED-9 and Egl-1 as regulators of mitochondrial fission and fusion dynamics.
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.
Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
Petrina
P
Delivani
Colin
C
Adrain
Rebecca C
RC
Taylor
Patrick J
PJ
Duriez
Seamus J
SJ
Martin
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D045304:Cytochromes c / Q000378:metabolism; D020558:GTP Phosphohydrolases; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; C112486:EGL-1 protein, C elegans; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human