Apaf1 is required for mitochondrial pathways of apoptosis and brain development

Cell. 1998 Sep 18;94(6):739-50. doi: 10.1016/s0092-8674(00)81733-x.

Abstract

Apoptosis is essential for the precise regulation of cellular homeostasis and development. The role in vivo of Apaf1, a mammalian homolog of C. elegans CED-4, was investigated in gene-targeted Apaf1-/- mice. Apaf1-deficient mice exhibited reduced apoptosis in the brain and striking craniofacial abnormalities with hyperproliferation of neuronal cells. Apaf1-deficient cells were resistant to a variety of apoptotic stimuli, and the processing of Caspases 2, 3, and 8 was impaired. However, both Apaf1-/- thymocytes and activated T lymphocytes were sensitive to Fas-induced killing, showing that Fas-mediated apoptosis in these cells is independent of Apaf1. These data indicate that Apaf1 plays a central role in the common events of mitochondria-dependent apoptosis in most death pathways and that this role is critical for normal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptotic Protease-Activating Factor 1
  • Brain / cytology*
  • Brain / embryology*
  • Brain Chemistry / physiology
  • Caspase 2
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases*
  • Cells, Cultured
  • Cysteine Endopeptidases / metabolism
  • Cytochrome c Group / metabolism
  • Embryo, Mammalian / abnormalities
  • Enzyme Precursors / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • Gene Expression
  • Head / abnormalities
  • Membrane Potentials / physiology
  • Mice
  • Mice, Knockout
  • Mitochondria / enzymology*
  • Phenotype
  • Proteins / genetics*
  • Proteins / immunology
  • Proteins / metabolism
  • Skin Abnormalities
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / cytology
  • T-Lymphocytes / radiation effects
  • Thymus Gland / chemistry
  • Thymus Gland / cytology
  • Thymus Gland / radiation effects
  • Ultraviolet Rays
  • fas Receptor / physiology

Substances

  • Apaf1 protein, mouse
  • Apoptotic Protease-Activating Factor 1
  • Cytochrome c Group
  • Enzyme Precursors
  • Proteins
  • fas Receptor
  • Casp3 protein, mouse
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 2
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cysteine Endopeptidases