TY - JOUR T1 - Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. AU - Deng,Xinzhu, AU - Yin,Xianglei, AU - Allan,Richard, AU - Lu,Diane D, AU - Maurer,Carine W, AU - Haimovitz-Friedman,Adriana, AU - Fuks,Zvi, AU - Shaham,Shai, AU - Kolesnick,Richard, PY - 2008/10/4/pubmed PY - 2008/10/22/medline PY - 2008/10/4/entrez SP - 110 EP - 5 JF - Science (New York, N.Y.) JO - Science VL - 322 IS - 5898 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/18832646/Ceramide_biogenesis_is_required_for_radiation_induced_apoptosis_in_the_germ_line_of_C__elegans_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=18832646 DB - PRIME DP - Unbound Medicine ER -