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

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 25; no. 5; pp. 259 - 264
• Main Authors: Hong, Suk Jin, Dawson, Ted M., Dawson, Valina L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2004
• Subjects: Apoptosis Inducing Factor; Caspases - metabolism; Caspases - physiology; Cell Death - physiology; Flavoproteins - physiology; Humans; Membrane Proteins - physiology; Mitochondria - enzymology; Mitochondria - metabolism; Mitochondria - physiology; Poly(ADP-ribose) Polymerases - physiology
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2004.03.005

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.