GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization.
Oncogene
; 26(18): 2606-20, 2007 Apr 19.
Article
em En
| MEDLINE
| ID: mdl-17072346
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a pleiotropic enzyme that is overexpressed in apoptosis and in several human chronic pathologies. Here, we report that the protein accumulates in mitochondria during apoptosis, and induces the pro-apoptotic mitochondrial membrane permeabilization, a decisive event of the intrinsic pathway of apoptosis. GAPDH was localized by immunogold labeling and identified by matrix-assisted laser desorption/ionization-time of flight and nano liquid chromatography mass spectroscopy/mass spectroscopy in the mitochondrion of various tissues and origins. In isolated mitochondria, GAPDH can be imported and interact with the voltage-dependent anion channel (VDAC1), but not the adenine nucleotide translocase (ANT). The protein mediates a cyclosporin A-inhibitable permeability transition, characterized by a loss of the inner transmembrane potential, matrix swelling, permeabilization of the inner mitochondrial membrane and the release of two pro-apoptotic proteins, cytochrome c and apoptosis-inducing factor (AIF). This novel function of GAPDH might have implications for the understanding of mitochondrial biology, oncogenesis and apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mitocôndrias Hepáticas
/
Permeabilidade da Membrana Celular
/
Apoptose
/
Membranas Mitocondriais
/
Gliceraldeído-3-Fosfato Desidrogenases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
Reino Unido