Mitochondrial and nuclear cross talk in cell death: Parthanatos

Shaida A. Andrabi, Ted M. Dawson, Valina L. Dawson

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair. Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood. Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer. Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death. Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death. This form of cell death is distinct from apoptosis, necrosis, or autophagy and is termed parthanatos. PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues. The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.

Original languageEnglish (US)
Title of host publicationMitochondria and Oxidative Stress in Neurodegenerative Disorders
PublisherBlackwell Publishing Inc.
Pages233-241
Number of pages9
ISBN (Print)9781573317139
DOIs
StatePublished - Dec 2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1147
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Apoptosis inducing factor
  • Excitotoxicity
  • Glutamate
  • Neurodegeneration
  • PARP-1
  • Parthanatos

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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