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

Overview

MeSH Major

  • Apoptosis
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Ceramides
  • Germ Cells
  • Radiation, Ionizing

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.

publication date

  • October 3, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2585063

Digital Object Identifier (DOI)

  • 10.1126/science.1158111

PubMed ID

  • 18832646

Additional Document Info

start page

  • 110

end page

  • 5

volume

  • 322

number

  • 5898