Protein of life, protein of death

[iansmith]

The same enzyme regulates programmed cell death and embryonic development | By Andrea Rinaldi


Complex, multicellular organisms must finely regulate their inner environment to assure cells can thrive, but must also initiate apoptosis (programmed cell death) when necessary. Apoptosis is critical for normal development and tissue homeostasis, and aberrant apoptosis can lead to cancer and neural degeneration. In a PNAS article published online December 8, Jianhua Zhang and colleagues at the University of Cincinnati College of Medicine pinpoint an enzyme that plays an important role in both the regulation of normal apoptosis and embryogenesis in mammals (PNAS, DOI:10.1073/pnas.2636393100, December 8, 2003).

Zhang et al. investigated the in vivo function of endonuclease G (EndoG), a mitochondrial protein encoded in the nucleus, previously reported to be important for nuclear DNA fragmentation during apoptosis and mitochondrial DNA replication. The authors studied the consequences of EndoG deficiency in mice and observed that homozygous mutant embryos died early during development and had lost normal morphology, while heterozygous animals developed normally. Mitochondrial numbers were the same in mutant and wildtype mice, suggesting that EndoG is not involved in mitochondrial DNA replication. The authors also observed that EndoG mutant cells subjected to apoptotic stimuli were more resistant to cell death than wildtype control cells.

In addition, Zhang et al. examined the effects on cell death of having EndoG mutation in cells that also lacked both genes for the DNA fragmentation factor (DFF), a protein identified by previous studies as important for DNA fragmentation during apoptosis. Efficient apoptosis required both DFF and EndoG, but DFF was identified as the predominant DNA fragmentation enzyme.

“These results suggest that DFF plays the more prominent role in DNA fragmentation and apoptosis in mammals and that EndoG likely facilitates DFF function in DNA fragmentation and apoptosis in vivo,” conclude the authors. Together, the findings of Zhang et al. indicate that EndoG is required for both embryogenesis and normal apoptosis. In particular, authors claim that EndoG may play an essential role in remodeling the embryo through apoptosis at the blastocyst stage, when cavitation occurs that converts a solid embryo into a hollow, two-layered egg cylinder.

http://www.biomedcentral.com/news/20031209/02

 

[chroot]

Seems like all the apoptosis factors (like AIF) are necessary for life... interesting, isn't it? I wonder if we'll make any progress on our quest for immortality with these kinds of roadblocks.

- Warren

 

[iansmith]

Scientist new that apoptosis was important during embryogenesis but I think that the importance migth be greater than we thought.

This is by not mean a roadblock to me for the quest to delaye aging, it is just a unexpected detour we have to take.

 

[Monique]

Some scientists have proposed that our age limit is set in our lysosomes, how well we are able to regenerate and refresh all the biomolecules in our cells. Think about your neurons, those have to live for 70 years and not with the same constituents that you were born with. I have got a number somewhere how fast the proteins on a membrane get regenerated, I'll have to look that up.

When the lysosomes start to accumulate waste materials, a cell begins to function less efficiently and will eventually die. I have never heard of any research into this mechanism of death, but if we have the quest for immortality, this would be an important thing to consider.