title: Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling.
abstract: 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.
authors.affiliation: Institute for Cell Engineering and Department of Neurology, Johns Hopkins University School of Medicine, 733 North Broadway Street, Suite 731, Baltimore, MD 21205, USA.
authors.forename: Suk Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
mesh_terms: D051033:Apoptosis Inducing Factor; D020169:Caspases / Q000378:metabolism* / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D005420:Flavoproteins / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases