Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis

BMC Cell Biol. 2013 Jul 9:14:32. doi: 10.1186/1471-2121-14-32.

Abstract

Background: Apoptosis is a form of programmed cell death that is regulated by the Bcl-2 family and caspase family of proteins. The caspase cascade responsible for executing cell death following cytochrome c release is well described; however the distinct roles of caspases-9, -3 and -7 during this process are not completely defined.

Results: Here we demonstrate several unique functions for each of these caspases during cell death. Specific inhibition of caspase-9 allows for efficient release of cytochrome c, but blocks changes in mitochondrial morphology and ROS production. We show that caspase-9 can cleave Bid into tBid at amino acid 59 and that this cleavage of Bid is required for ROS production following serum withdrawal. We also demonstrate that caspase-3-deficient MEFs are less sensitive to intrinsic cell death stimulation, yet have higher ROS production. In contrast, caspase-7-deficient MEFs are not resistance to intrinsic cell death, but remain attached to the ECM.

Conclusions: Taken together, these data suggest that caspase-9 is required for mitochondrial morphological changes and ROS production by cleaving and activating Bid into tBid. After activation by caspase-9, caspase-3 inhibits ROS production and is required for efficient execution of apoptosis, while effector caspase-7 is required for apoptotic cell detachment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • B-Lymphocytes / pathology*
  • B-Lymphocytes / physiology
  • Caspase 3 / physiology*
  • Caspase 7 / physiology*
  • Caspase 9 / physiology*
  • Cell Line
  • Cells, Cultured
  • Cytochromes c / physiology
  • Extracellular Matrix / physiology
  • Fibroblasts / pathology*
  • Fibroblasts / physiology
  • Mice
  • Mitochondria / physiology
  • Models, Animal
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Cytochromes c
  • Caspase 3
  • Caspase 7
  • Caspase 9