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

Matthew Brentnall1, Luis Rodriguez-Menocal, Rebeka Ladron De Guevara

  • 1Departments of Hematology and Medical Oncology and Cell Biology, Winship Cancer Institute of Emory University, 1365 Clifton Road NE Bldg:C, Rm:4012, Atlanta, GA 30322, USA.

BMC Cell Biology
|July 10, 2013
PubMed
Abstract

Insights

Caspase-9 initiates apoptosis by cleaving Bid, impacting mitochondrial changes and ROS production. Caspase-3 then inhibits ROS and executes cell death, while caspase-7 causes cell detachment.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Apoptosis, or programmed cell death, is regulated by Bcl-2 and caspase protein families.
  • The caspase cascade, including caspases-9, -3, and -7, executes cell death after cytochrome c release.
  • Distinct roles of caspases-9, -3, and -7 in apoptosis remain incompletely defined.

Purpose of the Study:

  • To elucidate the specific functions of caspases-9, -3, and -7 in the apoptotic process.
  • To investigate the role of caspase-9 in mitochondrial morphology and ROS production.
  • To define the contribution of caspase-3 and caspase-7 to intrinsic cell death and cell detachment.

Main Methods:

  • Utilizing specific caspase inhibitors to block enzymatic activity.
  • Employing caspase-deficient mouse embryonic fibroblasts (MEFs) to assess cell death pathways.
  • Analyzing mitochondrial morphology, reactive oxygen species (ROS) production, and cell-extracellular matrix interactions.

Main Results:

  • Caspase-9 inhibition prevented mitochondrial changes and ROS production despite cytochrome c release.
  • Caspase-9 directly cleaved Bid to tBid, a crucial step for ROS generation.
  • Caspase-3 deficiency led to reduced intrinsic cell death sensitivity but increased ROS production.
  • Caspase-7 deficiency did not affect intrinsic cell death but impaired apoptotic cell detachment.

Conclusions:

  • Caspase-9 is essential for initiating apoptosis-associated mitochondrial alterations and ROS production via Bid cleavage.
  • Caspase-3, activated by caspase-9, suppresses ROS and drives efficient apoptosis execution.
  • Caspase-7 plays a distinct role in facilitating apoptotic cell detachment from the extracellular matrix.

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