There may be 101 ways to kill a cell, but for each there is an escape route. Cells that escape apoptosis, report Anna Colell (Institut d'Investigacions Biomediques de Barcelona, Spain), Jean-Ehrland Ricci (Université de Nice Sophia-Antipolis, France), Douglas Green (St Jude's Children's Research Hospital, Memphis, TN), and colleagues, also have a way to escape the back-up killing mechanism that kicks in.
An early step in apoptosis is the permeabilization of mitochondrial membranes. Mitochondria then lose cytochrome C, which triggers caspase activation and death. For cells that manage to inhibit caspases, there is always plan B—caspase-independent cell death (CICD).
An escape from CICD has been reported for starving neurons, but it's also possible that defeating CICD might be one way to transform cancer cells.
Colell et al. screened a cDNA library for genes that protected cells from CICD. They found GAPDH. High levels of this enzyme led to increases in glycolysis and ATP levels and also to autophagy. The team showed that GAPDH increased the expression of an autophagy-promoting gene.
Both glycolysis and autophagy were necessary for protection from CICD. Evidence also suggests that autophagosomes might be gobbling up the defective mitochondria. Thus the rise in GAPDH might provide energy for both mitochondrial repair and clearing up damaged mitochondrial remains.