The BCL-2-like protein CED-9 of C. elegans promotes FZO-1/Mfn1,2- and EAT-3/Opa1-dependent mitochondrial fusion.
The mammalian dynamin-related guanosine triphosphatases Mfn1,2 and Opa1 are required for mitochondrial fusion. However, how their activities are controlled and coordinated is largely unknown. We present data that implicate the BCL-2-like protein CED-9 in the control of mitochondrial fusion in Caenorhabditis elegans. We demonstrate that CED-9 can promote complete mitochondrial fusion of both the outer and inner mitochondrial membrane. We also show that this fusion is dependent on the C. elegans Mfn1,2 homologue FZO-1 and the C. elegans Opa1 homologue EAT-3. Furthermore, we show that CED-9 physically interacts with FZO-1 in vivo and that the ability of CED-9 to interact with FZO-1 is important for its ability to cause mitochondrial fusion. CED-9-induced mitochondrial fusion is not required for the maintenance of mitochondrial morphology during embryogenesis or in muscle cells, at least under normal conditions and in the absence of stress. Therefore, we propose that the BCL-2-like CED-9 acts through FZO-1/Mfn1,2 and EAT-3/Opa1 to promote mitochondrial fusion in response to specific cellular signals.
Rolland
Stéphane G
SG
Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03755, USA.
Lu
Yun
Y
David
Charles N
CN
Conradt
Barbara
B
D000818:Animals; D030801:Animals, Genetically Modified; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D064550:Death-Associated Protein Kinases; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C543815:EAT-3 protein, C elegans; C543814:FZO-1 protein, C elegans; D020558:GTP Phosphohydrolases
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