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Article Dans Une Revue Cell Année : 2007

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

Résumé

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.

Dates et versions

hal-00166141 , version 1 (01-08-2007)

Identifiants

Citer

Anna Colell, Jean-Ehrland Ricci, Stephen Tait, Sandra Milasta, Ulrich Maurer, et al.. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation.. Cell, 2007, 129 (5), pp.983-97. ⟨10.1016/j.cell.2007.03.045⟩. ⟨hal-00166141⟩
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