GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation

Colell, A. et al. (2007) GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell, 129(5), pp. 983-997. (doi: 10.1016/j.cell.2007.03.045)

Abstract

In cells undergoing apoptosis, mitochondrial outer-membrane permeabilization (MOMP) is followed by caspase activation promoted by released cytochrome c. Although caspases mediate the apoptotic phenotype, caspase inhibition is generally not sufficient for survival following MOMP; instead cells undergo a “caspase-independent cell death” (CICD). Thus, MOMP may represent a point of commitment to cell death. Here, we identify glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a critical regulator of CICD. GAPDH-expressing cells preserved their clonogenic potential following MOMP, provided that caspase activation was blocked. GAPDH-mediated protection of cells from CICD involved an elevation in glycolysis and a nuclear function that correlated with and was replaced by an increase in Atg12 expression. Consistent with this, protection from CICD reflected an increase in and a dependence upon autophagy, associated with a transient decrease in mitochondrial mass. Therefore, GAPDH mediates an elevation in glycolysis and enhanced autophagy that cooperate to protect cells from CICD.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tait, Professor Stephen
• Authors: Colell, A., Ricci, J.-E., Tait, S.W.G., Milasta, S., Maurer, U., Bouchier-Hayes, L., Fitzgerald, P., Guio-Carrion, A., Waterhouse, N.J., Li, C.W., Mari, B., Barbry, P., Newmeyer, D.D., Beere, H.M., and Green, D.R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell
• ISSN: 0092-8674
• ISSN (Online): 1097-4172
• Published Online: 31 May 2007