title: CED-9 and mitochondrial homeostasis in C. elegans muscle.
abstract: 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.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Tan
authors.forename: Michelle
authors.initials: M
authors.lastname: Husain
authors.forename: Cara Marie
authors.initials: CM
authors.lastname: Manlandro
authors.forename: Marijke
authors.initials: M
authors.lastname: Koppenol
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Fire
authors.forename: R Blake
authors.initials: RB
authors.lastname: Hill
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins