GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation.
Cell
; 129(5): 983-97, 2007 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-17540177
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Sobrevivência Celular
/
Apoptose
/
Gliceraldeído-3-Fosfato Desidrogenases
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article