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Exp Neurol. 2009 Aug;218(2):193-202. doi: 10.1016/j.expneurol.2009.03.020. Epub 2009 Mar 28.

Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos.

Author information

1
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in multiple neurologic diseases by mediating caspase-independent cell death, which has recently been designated parthanatos to distinguish it from other forms of cell death such as apoptosis, necrosis and autophagy. Mitochondrial apoptosis-inducing factor (AIF) release and translocation to the nucleus is the commitment point for parthanatos. This process involves a pathogenic role of poly(ADP-ribose) (PAR) polymer. It generates in the nucleus and translocates to the mitochondria to mediate AIF release following lethal PARP-1 activation. PAR polymer itself is toxic to cells. Thus, PAR polymer signaling to mitochondrial AIF is the key event initiating the deadly crosstalk between the nucleus and the mitochondria in parthanatos. Targeting PAR-mediated AIF release could be a potential approach for the therapy of neurologic disorders.

PMID:
19332058
PMCID:
PMC2752872
DOI:
10.1016/j.expneurol.2009.03.020
[Indexed for MEDLINE]
Free PMC Article

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