Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / physiology
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Caenorhabditis elegans / embryology
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / ultrastructure
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Caenorhabditis elegans Proteins / genetics*
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Caenorhabditis elegans Proteins / metabolism
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Caenorhabditis elegans Proteins / physiology
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Caspases / genetics
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Caspases / metabolism
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Cells, Cultured
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Cryoelectron Microscopy / methods
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Genetic Complementation Test
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Germ Cells / cytology
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Germ Cells / metabolism
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Germ Cells / ultrastructure
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Gonads / cytology
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Gonads / metabolism
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Gonads / ultrastructure
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Green Fluorescent Proteins / analysis
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Green Fluorescent Proteins / genetics
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Humans
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Immunohistochemistry
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Microscopy, Fluorescence
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Mitochondrial Membranes / metabolism*
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Mitochondrial Membranes / physiology
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Mitochondrial Membranes / ultrastructure
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Models, Genetic
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Morphogenesis / genetics
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Morphogenesis / physiology
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Mutation / genetics
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Oogenesis / genetics
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Oogenesis / physiology
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RNA Interference / physiology
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Recombinant Fusion Proteins / analysis
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Recombinant Fusion Proteins / genetics
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Tumor Suppressor Proteins / physiology
Substances
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Caenorhabditis elegans Proteins
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Recombinant Fusion Proteins
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Tumor Suppressor Proteins
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Green Fluorescent Proteins
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Caspases
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ced-3 protein, C elegans