Caenorhabditis elegans par2.1/mtssb-1 is essential for mitochondrial DNA replication and its defect causes comprehensive transcriptional alterations including a hypoxia response

Tomoko Sugimoto, Chihiro Mori, Takako Takanami, Yohei Sasagawa, Rumiko Saito, Eiichiro Ichiishi, Atsushi Higashitani

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

DNA polymerase γ 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.

Original languageEnglish
Pages (from-to)103-114
Number of pages12
JournalExperimental Cell Research
Volume314
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1

Keywords

  • Apoptosis
  • DNA microarray
  • Ethidium bromide
  • Hypoxia response
  • Mitochondrial dysfunction
  • RNAi
  • ROS
  • mtSSB

ASJC Scopus subject areas

  • Cell Biology

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