Cytochrome c's ATP-binding sites (red and green) overlap with its Apaf1-binding sites (red).

TANG/ELSEVIER

Nucleotides are the building blocks of DNA and the cell's energy currency. Now, a report by Dhyan Chandra, Dean Tang (University of Texas, Smithville, TX), and colleagues reveals that these multifunctional molecules are also bodyguards, protecting healthy cells from apoptosis.

The apoptotic cascade unfolds when failing mitochondria leak cytochrome c (cyt c), which then binds to and oligomerizes the caspase activator called Apaf1. Previous experiments showed that low concentrations of nucleotides, in the form of ATP or dATP, were needed for cyt c to bind to Apaf1.

The new results show that higher concentrations of ATP prevent apoptosis. At these higher levels, which match those found in healthy cells, the nucleotides bound up cyt c, thus preventing it from attaching to its Apaf1 partner.

The inhibition was overcome...

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