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 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 32" - "Export Date: 17 November 2011" - "CODEN: SCIEA" - "Source: Scopus" |
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