title: A molecular switch that governs mitochondrial fusion and fission mediated by the BCL2-like protein CED-9 of Caenorhabditis elegans.
abstract: Depending on the cellular context, BCL2-like proteins promote mitochondrial fusion or fission. What determines which of these two opposing processes they promote has so far been unknown. Furthermore, the mechanisms through which BCL2-like proteins affect mitochondrial dynamics remain to be fully understood. The BCL2-like protein CED-9 of Caenorhabditis elegans has previously been shown to promote mitochondrial fusion by physically interacting with the mitochondrial fusion protein FZO-1. Here, we report that CED-9 also physically interacts with the mitochondrial fission protein DRP-1 and that this interaction can be enhanced when CED-9 is associated with the BH3-only protein EGL-1. In addition, we show that the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting DRP-1 to mitochondria and that the egl-1 gene is required for CED-9-dependent mitochondrial fission in vivo. Based on these results, we propose that EGL-1 converts CED-9 into a mitochondrial receptor for DRP-1, thereby shifting its activity from profusion to profission. We hypothesize that BCL2-like proteins act as mitochondrial receptors for DRP-1-like proteins in higher organisms as well and that BH3-only proteins play a general role as modifiers of the function in mitochondrial dynamics of BCL2-like proteins. We speculate that this function of BCL2-like proteins may be as couplers of mitochondrial fusion and fission.
authors.affiliation: Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.forename: Stéphane G
authors.initials: SG
authors.lastname: Rolland
authors.forename: Barbara
authors.initials: B
authors.lastname: Conradt
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; C087233:Ced-9 protein, C elegans; C112486:EGL-1 protein, C elegans; D046912:Multiprotein Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D006160:Guanosine Triphosphate; C543814:FZO-1 protein, C elegans; D020558:GTP Phosphohydrolases; D034281:Dynamins