Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling.


Different cell-death mechanisms control many physiological and pathological processes in humans. Mitochondria play important roles in cell death through the release of pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor (AIF), which activate caspase-dependent and caspase-independent cell death, respectively. Poly(ADP-ribose) polymerase 1 (PARP-1) is emerging as an important activator of caspase-independent cell death. PARP-1 generates the majority of long, branched poly(ADP-ribose) (PAR) polymers following DNA damage. Overactivation of PARP-1 initiates a nuclear signal that propagates to mitochondria and triggers the release of AIF. AIF then shuttles from mitochondria to the nucleus and induces peripheral chromatin condensation, large-scale fragmentation of DNA and, ultimately, cytotoxicity. Identification of the pro-death and pro-survival signals in the PARP-1-mediated cell-death program might provide novel therapeutic targets in human diseases.

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@article{Hong2004NuclearAM, title={Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling.}, author={Suk Jin Hong and Ted M Dawson and Valina L Dawson}, journal={Trends in pharmacological sciences}, year={2004}, volume={25 5}, pages={259-64} }