Caenorhabditis elegans ATR checkpoint kinase ATL-1 influences life span through mitochondrial maintenance

Kazuhiro Suetomi, Stefan Mereiter, Chihiro Mori, Takako Takanami, Atsushi Higashitani

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    ATR is highly conserved in all eukaryotes and functions as a cell-cycle nuclear checkpoint kinase. In mammals, ATR is essential whose complete absence results in early embryonic lethality and its hypomorphic mutation causes a complex disease known as Seckel syndrome. However, molecular mechanisms that cause a wide variety of symptoms including accelerated aging have remained unclear. Similarly, in the nematode Caenorhabditis elegans, a deletion mutant of ATR ortholog atl-1 appears to develop into normal adults, but their eggs do not hatch and die at early embryogenesis. Here we show that the parental worms of atl-1 defective mutant achieved longevity. Transcription levels of certain superoxide dismutase genes, sod-3 and -5 and enzymatic activity of superoxide dismutases significantly increased in the mutant. Furthermore, lipid peroxidation such as a formation of malondialdehyde was attenuated. Expressions of other genes regulated by DAF-16/FOXO transcription factor were also altered. In contrast, the mutant became hypersensitive to rotenone and ethidium bromide. Compared with the wild type the mitochondrial DNA copy number in the mutant was lesser and its proliferation is more severely inhibited in the presence of rotenone. These results suggest that C. elegans ATL-1 is involved not only in the nuclear checkpoint control but also in the mitochondrial maintenance, and its dysfunction activates mild oxidative stress response, resulting in an alteration of life span.

    Original languageEnglish
    Pages (from-to)729-735
    Number of pages7
    JournalMitochondrion
    Volume13
    Issue number6
    DOIs
    Publication statusPublished - 2013 Nov 1

    Keywords

    • Ataxia telangiectasia
    • DAF-16
    • Ethidium bromide
    • Longevity
    • Rotenone
    • SOD

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Cell Biology

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