Apaf1 Is Required for Mitochondrial Pathways of Apoptosis and Brain Development

@article{Yoshida1998Apaf1IR,
  title={Apaf1 Is Required for Mitochondrial Pathways of Apoptosis and Brain Development},
  author={Hiroki Yoshida and Young-Yun Kong and Ritsuko Yoshida and Andrew J. Elia and Anne Hakem and Razqallah Hakem and Josef M. Penninger and Tak Wah Mak},
  journal={Cell},
  year={1998},
  volume={94},
  pages={739-750}
}
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… 
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TLDR
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Specific Ablation of the Apoptotic Functions of Cytochrome c Reveals a Differential Requirement for Cytochrome c and Apaf-1 in Apoptosis
TLDR
The studies indicate the existence of a Cyt c- and apoptosome-independent but Apaf-1-dependent mechanism(s) for caspase activation and fibroblasts from the KA/KA mice were resistant to apoptosis, their thymocytes were markedly more sensitive to death stimuli than Apaf.
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TLDR
Non-apoptotic cell death in NPCs may be a compensatory mechanism in the developing CNS of Apaf1-deficient embryos and ROS generation may partially participate in the cell death.
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TLDR
The mitochondria-mediated apoptosis pathway is discussed and its physiological roles and therapeutic implications are discussed, showing that cytochrome c release from mitochondria does not always lead to irreversible cell death, and that caspase activation can also have non-death functions.
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A population of neurons in the developing brain that are acutely dependent on Bcl-xL during the peak period of synaptic connectivity that are important for the establishment of higher-order complex behaviors is identified.
Differential requirement for the mitochondrial apoptosis-inducing factor in apoptotic pathways
TLDR
It is shown that AIF is required for cell death in response to serum withdrawal, but not to DNA damage or inhibition of kinases, providing the first genetic evidence for a caspaseindependent pathway of PCD.
Embryonic neuronal death due to neurotrophin and neurotransmitter deprivation occurs independent of Apaf-1
TLDR
It is proposed that a switch between apoptotic programs (and their respective proteins) characterizes the transition of a neuronal precursor cell from the progenitor pool to the postmitotic population of differentiated neurons.
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