A caspase-independent apoptosis pathway

In animals the process of programmed cell death, or apoptosis, is thought to be mediated by caspases, a family of cysteine proteases that cleave one another and key intracellular proteins, killing the cell in a controlled way. In 29 March Nature, Nicholas Joza and colleagues at the Amgen Institute, Toronto, Canada provide genetic evidence that the first wave of apoptosis in the early mouse embryo requires a molecule called apoptosis-inducing factor (AIF) and not caspases (Nature 2001, 410:549-554).

Joza et al deleted exon 3 of the aif gene in mouse embryonic stem (ES) cells. This exon encodes the amino terminus of the protein, and because the aif gene is on the X chromosome, mutation of one aif allele resulted in a complete knockout in male ES cells. The resulting mutant cells were defective in apoptosis. In the absence of serum normal cells in culture commit suicide, but aif–/Y ES cells ...