title: GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation.
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.
authors.affiliation: Department of Cell Death and Proliferation, Institut d'Investigacions Biomediques de Barcelona (IIBB-CSIC), IDIBAPS, 08036 Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Colell
authors.forename: Jean-Ehrland
authors.initials: JE
authors.lastname: Ricci
authors.forename: Stephen
authors.initials: S
authors.lastname: Tait
authors.forename: Sandra
authors.initials: S
authors.lastname: Milasta
authors.forename: Ulrich
authors.initials: U
authors.lastname: Maurer
authors.forename: Lisa
authors.initials: L
authors.lastname: Bouchier-Hayes
authors.forename: Patrick
authors.initials: P
authors.lastname: Fitzgerald
authors.forename: Ana
authors.initials: A
authors.lastname: Guio-Carrion
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Waterhouse
authors.forename: Cindy Wei
authors.initials: CW
authors.lastname: Li
authors.forename: Bernard
authors.initials: B
authors.lastname: Mari
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.forename: Donald D
authors.initials: DD
authors.lastname: Newmeyer
authors.forename: Helen M
authors.initials: HM
authors.lastname: Beere
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D034622:RNA Interference
chemical_list: D045304:Cytochromes c; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D020169:Caspases