Cell Biology

Apoptosis by Another Route

Science Signaling  07 Oct 2008:
Vol. 1, Issue 40, pp. ec350
DOI: 10.1126/scisignal.140ec350

The sphingolipid ceramide has been implicated in the regulation of apoptosis, but its importance has been debated. Deng et al. provide strong evidence for a role for ceramide in regulating a particular form of apoptosis—that of germ cells in the worm Caenorhabditis elegans that have been exposed to ionizing radiation—but not in apoptosis that occurs normally during development. Mutant animals that lacked function of ceramide synthase (the enzyme that produces ceramide) were deficient in radiation-induced apoptosis. Although the precise molecular role of ceramide remains uncertain, it appears to act at the mitochondria. Ceramide accumulated at the mitochondria of germ cells from irradiated animals. Production of ceramide was also necessary for redistribution of the APAF-1 (apoptotic protease activating factor 1)–like protein CED-4 from the mitochondria to the nucleus, where it activates the caspase CED3. Thus, ceramide may act by altering the properties of the mitochondrial outer membrane where key regulatory proteins controlling apoptosis interact.

X. Deng, X. Yin, R. Allan, D. D. Lu, C. W. Maurer, A. Haimovitz-Friedman, Z. Fuks, S. Shaham, R. Kolesnick, Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science 322, 110-115 (2008). [Abstract] [Full Text]