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.
Han
Sung Min
SM
Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, Korea.
Lee
Tae Hoon
TH
Mun
Ji Young
JY
Kim
Moon Jeong
MJ
Kritikou
Ekaterini A
EA
Lee
Se-Jin
SJ
Han
Sung Sik
SS
Hengartner
Michael O
MO
Koo
Hyeon-Sook
HS
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020285:Cryoelectron Microscopy / Q000379:methods; D005816:Genetic Complementation Test; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006066:Gonads / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D008957:Models, Genetic; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D020169:Caspases; C089223:ced-3 protein, C elegans