Reference - Detail
|Author||Han SM, Lee TH, Mun JY, Kim MJ, Kritikou EA, Lee SJ, Han SS, Hengartner MO, Koo HS.|
|Title||Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans.|
DICE1 (deleted in cancer 1), first identified in human lung carcinoma cell lines, is a candidate tumor suppressor, but the details of its activity remain largely unknown. We have found that RNA interference of its C. elegans homolog (DIC-1) produced inviable embryos with increased apoptosis, cavities in cells and abnormal morphogenesis. In the dic-1(RNAi) germ line, ced-3-dependent apoptosis increased, and cell cavities appeared at the late-pachytene/oogenic stage, leading to defective oogenesis. Immunofluorescence microscopy of DIC-1 revealed its ubiquitous expression in the form of cytoplasmic foci, and cryoelectron microscopy narrowed down the location of the foci to the inner membrane of mitochondria. After dic-1 RNAi, mitochondria had an irregular morphology and contained numerous internal vesicles. Homozygous embryos from a heterozygous dic-1 mother arrested at the L3 larval stage, in agreement with the essential role of DIC-1 in mitochondria. In summary, C. elegans DIC-1 plays a crucial role in the formation of normal morphology of the mitochondrial cristae/inner membrane. Our results suggest that human DICE1 may have several functions in multiple intracellular locations.
|MeSH||Animals Apoptosis / genetics Apoptosis / physiology Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology Caspases / genetics Caspases / metabolism Cells, Cultured Cryoelectron Microscopy / methods Genetic Complementation Test Germ Cells / cytology Germ Cells / metabolism Germ Cells / ultrastructure Gonads / cytology Gonads / metabolism Gonads / ultrastructure Green Fluorescent Proteins / analysis Green Fluorescent Proteins / genetics Humans Immunohistochemistry Microscopy, Fluorescence Mitochondrial Membranes / metabolism* Mitochondrial Membranes / physiology Mitochondrial Membranes / ultrastructure Models, Genetic Morphogenesis / genetics Morphogenesis / physiology Mutation / genetics Oogenesis / genetics Oogenesis / physiology RNA Interference / physiology Recombinant Fusion Proteins / analysis Recombinant Fusion Proteins / genetics Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism Tumor Suppressor Proteins / physiology|
|WOS Category||DEVELOPMENTAL BIOLOGY|