GAPDH and Autophagy Preserve Survival after Apoptotic Cytochrome c Release in the Absence of Caspase Activation

347Citations
Citations of this article
260Readers
Mendeley users who have this article in their library.

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. © 2007 Elsevier Inc. All rights reserved.

Author supplied keywords

Cite

CITATION STYLE

APA

Colell, A., Ricci, J. E., Tait, S., Milasta, S., Maurer, U., Bouchier-Hayes, L., … Green, D. R. (2007). GAPDH and Autophagy Preserve Survival after Apoptotic Cytochrome c Release in the Absence of Caspase Activation. Cell, 129(5), 983–997. https://doi.org/10.1016/j.cell.2007.03.045

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free