Portrait of a killer: the mitochondrial apoptosome emerges from the shadows

Michelle M Hill, Colin Adrain, Seamus J Martin

Research output: Contribution to journalReview articlepeer-review

81 Citations (Scopus)

Abstract

Apoptosis (programmed cell death) is a physiological process used to eliminate superfluous, damaged, infected, or aged cells in multicellular organisms. During apoptosis the cellular architecture is dismantled from within in a highly controlled fashion. Members of the caspase family of cysteine proteases are responsible for the destructive phase of apoptosis. One major pathway to caspase activation involves the formation of a multisubunit protease activation complex called the apoptosome. The apoptosome is assembled in response to signals that provoke mitochondrial outer membrane permeabilization and the release of cytochrome c into the cytosol. Recent studies indicate that the apoptosome is a wheel-like structure consisting of seven molecules of Apaf-1 and a similar number of caspase-9 dimers. Knowledge of the structure of the apoptosome will likely lead to the design of therapeutic modulators of apoptosis.

Original languageEnglish
Pages (from-to)19-26
Number of pages8
JournalMolecular interventions
Volume3
Issue number1
DOIs
Publication statusPublished - Feb 2003

Keywords

  • Apoptosis/physiology
  • Apoptotic Protease-Activating Factor 1
  • Caspase 9
  • Caspases/chemistry
  • Cytochrome c Group/physiology
  • Deoxyadenine Nucleotides/metabolism
  • Dimerization
  • Enzyme Activation
  • Humans
  • Mitochondria/metabolism
  • Models, Molecular
  • Proteins/chemistry

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