Biochemical pathways of caspase activation during apoptosis

I. Budihardjo, H. Oliver, M. Lutter, X. Luo, X. Wang

Research output: Contribution to journalReview articlepeer-review

2323 Scopus citations


Caspase activation plays a central role in the execution of apoptosis. The key components of the biochemical pathways of caspase activation have been recently elucidated. In this review, we focus on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway and the mitochondria-initiated pathway. In the cell surface death receptor pathway, activation of caspase-8 following its recruitment to the death-inducing signaling complex (DISC) is the critical event that transmits the death signal. This event is regulated at several different levels by various viral and mammalian proteins. Activated caspase-8 can activate downstream caspases by direct cleavage or indirectly by cleaving Bid and inducing cytochrome c release from the mitochondria. In the mitochondrial-initiated pathway, caspase activation is triggered by the formation of a multimeric Apaf-1/cytochrome c complex that is fully functional in recruiting and activating procaspase-9. Activated caspase-9 will then cleave and activate downstream caspases such as caspase-3, -6, and -7. This pathway is regulated at several steps, including the release of cytochrome c from the mitochondria, the binding and hydrolysis of dATP/ATP by Apaf-1, and the inhibition of caspase activation by the proteins that belong to the inhibitors of apoptosis (IAP).

Original languageEnglish (US)
Pages (from-to)269-290
Number of pages22
JournalAnnual Review of Cell and Developmental Biology
StatePublished - 1999
Externally publishedYes


  • Apaf-1
  • Bcl-2
  • Cell surface death receptor
  • Cytochrome c
  • Mitochondria

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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