Xinzhu Deng et al. (2008) Development & Evolution Meeting "Ceramide Biogenesis is Required for Radiation-induced Apoptosisin the Germ Line of Caenorhabditis elegans"

Diane Lu, Adriana Haimovitz-Friedman, Shai Shaham, Xinzhu Deng, Richard Kolesnick, Carine Maurer, Richard Allan, Xianglei Yin, Zvi Fuks

[Development & Evolution Meeting, 2008]

Sphingolipids are important signaling molecules and the genes involved in sphinglipid biosynthesis are conserved between humans and C. elegans.In this study, we generated loss-of-function (lf) mutants of conserved genes of sphingolipid metabolism in C. elegans. We find that while somatic (developmental) apoptosis is unaffected, stress (ionizing radiation)-induced apoptosis of germ cells is obliterated upon inactivation of ceramide synthase, and restored upon microinjection of long chain natural ceramide. Ionizing radiation-induced ceramide elevation localized to mitochondria and was required for EGL-1-mediated CED-4 displacement from the CED-9/CED-4 complex, an obligate step in CED-3 caspase activation. These studies define CEP-1/p53-mediated EGL-1 upregulation and ceramide synthase-mediated ceramide generation on parallel pathways that integrate at mitochondrial membranes to co-regulate the stress-induced apoptotic checkpoint.