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First published online 16 August 2006
doi: 10.1242/dev.02534

Development 133, 3597-3606 (2006)
Published by The Company of Biologists 2006
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Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans

Sung Min Han1,*, Tae Hoon Lee1,*, Ji Young Mun2,*, Moon Jeong Kim1, Ekaterini A. Kritikou3, Se-Jin Lee1, Sung Sik Han2, Michael O. Hengartner3 and Hyeon-Sook Koo1,{dagger}

1 Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, Korea.
2 School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
3 Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland.

{dagger} Author for correspondence (e-mail: kooh{at}yonsei.ac.kr)

Accepted 13 July 2006

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.

Key words: DICE1 (INTS6), Apoptosis, Mitochondria, Cristae remodeling, C. elegans






© The Company of Biologists Ltd 2006