Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans Journal Article

Authors: Deng, X.; Yin, X.; Allan, R.; Lu, D. D.; Maurer, C. W.; Haimovitz-Friedman, A.; Fuks, Z.; Shaham, S.; Kolesnick, R.
Article Title: Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans
Abstract: Ceramide engagement in apoptotic pathways has been a topic of controversy. To address this controversy, we tested loss-of-function (lf) mutants of conserved genes of sphingolipid metabolism in Caenorhabditis elegans. Although somatic (developmental) apoptosis was unaffected, ionizing radiation-induced apoptosis of germ cells was obliterated upon inactivation of ceramide synthase and restored upon microinjection of long-chain natural ceramide. Radiation-induced increase in the concentration of ceramide localized to mitochondria and was required for BH3-domain protein EGL-1-mediated displacement of CED-4 (an APAF-1-like protein) from the CED-9 (a Bcl-2 family member)/CED-4 complex, an obligate step in activation of the CED-3 caspase. These studies define CEP-1 (the worm homolog of the tumor suppressor p53)-mediated accumulation of EGL-1 and ceramide synthase-mediated generation of ceramide through parallel pathways that integrate at mitochondrial membranes to regulate stress-induced apoptosis.
Keywords: unclassified drug; gene mutation; mutation; nonhuman; animals; apoptosis; protein; enzyme activity; caspase; radiation exposure; germ cells; germ line; enzyme inactivation; ionizing radiation; radiation, ionizing; tumor suppressor protein p53; calcium-binding proteins; caenorhabditis elegans; tumor; protein family; oxidoreductases; mitochondria; repressor proteins; lipid metabolism; proto-oncogene proteins c-bcl-2; mitochondrion; ceramide; ceramides; nematode; ceramide synthase; synthetase; caenorhabditis elegans proteins; genes, helminth; nuclear envelope; sphingolipid; mitochondrial membranes; proto-oncogene proteins c-abl
Journal Title: Science
Volume: 322
Issue: 5898
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2008-10-03
Start Page: 110
End Page: 115
Language: English
DOI: 10.1126/science.1158111
PUBMED: 18832646
PROVIDER: scopus
PMCID: PMC2585063
Notes: --- - "Cited By (since 1996): 32" - "Export Date: 17 November 2011" - "CODEN: SCIEA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Zvi Fuks
    309 Fuks
  2. Xianglei Yin
    9 Yin
  3. Richard N Kolesnick
    235 Kolesnick
  4. Xinzhu Deng
    10 Deng
  5. Richard Allan
    1 Allan
  6. Diane D Lu
    2 Lu