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.
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