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Tan, FJ, Husain, M, Manlandro, CM, Koppenol, M, Fire, AZ and Hill, RB (2008) CED-9 and mitochondrial homeostasis in C. elegans muscle. J. Cell. Sci. 121:3373-82


Mitochondrial homeostasis reflects a dynamic balance between membrane fission and fusion events thought essential for mitochondrial function. We report here that altered expression of the C. elegans BCL2 homolog CED-9 affects both mitochondrial fission and fusion. Although striated muscle cells lacking CED-9 have no alteration in mitochondrial size or ultrastructure, these cells appear more sensitive to mitochondrial fragmentation. By contrast, increased CED-9 expression in these cells produces highly interconnected mitochondria. This mitochondrial phenotype is partially suppressed by increased expression of the dynamin-related GTPase DRP-1, with suppression dependent on the BH3 binding pocket of CED-9. This suppression suggests that CED-9 directly regulates DRP-1, a model supported by our finding that CED-9 activates the GTPase activity of human DRP1. Thus, CED-9 is capable of regulating the mitochondrial fission-fusion cycle but is not essential for either fission or fusion.


PubMed PMC2785848 Online version:10.1242/jcs.032904


Animals; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; GTP Phosphohydrolases/genetics; GTP Phosphohydrolases/metabolism; Homeostasis/physiology; Humans; Membrane Fusion/physiology; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Mitochondria/genetics; Mitochondria/metabolism; Mitochondrial Membranes/metabolism; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Models, Biological; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism