Last Gasps for Cells

Science's STKE  16 Jul 2002:
Vol. 2002, Issue 141, pp. tw254
DOI: 10.1126/stke.2002.141.tw254

Without oxygen, cells in the brain and the heart die, but they do so by an ill-defined mechanism distinct from the well-studied apoptosis (programmed cell death). In this so-called necrotic cell death, DNA damage activates the enzyme poly(ADP-ribose) polymerase-1 (PARP-1). Yu et al. (see the Perspective by Chiarugi and Moskowitz) show that in an unexpected parallel to apoptosis, PARP-1 causes translocation of AIF (apoptosis inducing factor) to the nucleus, where it launches the cell on its death spiral by causing chromatin fragmentation. In true apoptosis, the key step is AIF translocation to the mitochondria, where it initiates the release of cytochrome c that in turn activates destructive proteases called caspases. Similar AIF action in mitochondria also occurs in necrosis, but it is a later, nonessential step.

S.-W. Yu, H. Wang, M. F. Poitras, C. Coombs, W. J. Bowers, H. J. Federoff, G. G. Poirier, T. M. Dawson, V. L. Dawson, Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297, 259-263 (2002). [Abstract] [Full Text]

A. Chiarugi, M. A. Moskowitz, PARP-1--a perpetrator of apoptotic cell death? Science 297, 200-201 (2002). [Abstract] [Full Text]