RRC ID 4303
Author Sugimoto T, Mori C, Takanami T, Sasagawa Y, Saito R, Ichiishi E, Higashitani A.
Title Caenorhabditis elegans par2.1/mtssb-1 is essential for mitochondrial DNA replication and its defect causes comprehensive transcriptional alterations including a hypoxia response.
Journal Exp. Cell Res.
Abstract DNA polymerase gamma and mtSSB are key components of the mtDNA replication machinery. To study the biological influences of defects in mtDNA replication, we used RNAi to deplete the gene for a putative mtSSB, par2.1, in Caenorhabditis elegans. In previous systematic RNAi screens, downregulation of this gene has not caused any clearly defective phenotypes. Here, we continuously fed a dsRNA targeting par2.1 to C. elegans over generations. Seventy-nine percent of F1 progeny produced 60-72 h after feeding grew to adulthood but were completely sterile, with an arrest of germline cell proliferation. Analyses of mtDNA copy number and cell cytology indicated that the sterile hermaphrodites had fewer mitochondria. These results indicated that par2.1 essentially functions for germline cell proliferation through mtDNA replication; we therefore termed it mtssb-1. Comprehensive transcriptional alterations including hypoxia response induction dependent on and independent of hif-1 function, occurred by RNAi depletion of mtssb-1. Treatment with ethidium bromide, which impairs mtDNA replication and transcription, caused similar transcriptional alterations. In addition, the frequency of apoptosis in the germline cells was reduced in fertile progeny with a partial RNAi effect. These suggest that RNAi depletion of C. elegans mtssb-1 is useful as a model system of mitochondrial dysfunction.
Volume 314(1)
Pages 103-14
Published 2008-1-1
DOI 10.1016/j.yexcr.2007.08.015
PII S0014-4827(07)00398-9
PMID 17900564
MeSH Animals Apoptosis / genetics Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Cell Proliferation DNA Replication / genetics* DNA, Mitochondrial / genetics* DNA-Binding Proteins / genetics* Down-Regulation / genetics Germ-Line Mutation / genetics Hypoxia / genetics* Hypoxia / metabolism Hypoxia / physiopathology Hypoxia-Inducible Factor 1 / genetics Infertility / genetics Mitochondria / genetics RNA Interference Regulatory Elements, Transcriptional / genetics Xenopus Proteins / genetics
IF 3.309
Times Cited 15
WOS Category ONCOLOGY CELL BIOLOGY
Resource
C.elegans tm2685