Gapdh, a Novel Regulator of the Pro-apoptotic Mitochondrial Membrane Permeabilization.
From: CNRS UMR 8159, Université de Versailles/SQY, Versailles, France.
Oncogene
- Publish Date: Apr 2007
- ISSN: 0950-9232
- Volume: 26
- Issue: 18
- Pages: 2606-20
- Medium: Print
- Language: English
- Citation (JAMA): Tarze A, Deniaud A, Le Bras M, et al. Gapdh, a Novel Regulator of the Pro-apoptotic Mitochondrial Membrane Permeabilization.. Oncogene Apr 2007;26:2606-20
Abstract
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.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Apoptosis, Caspase 3, Cell Membrane Permeability, Cells, Cultured, Colonic Neoplasms, Cyclosporine, Cytochromes c, Electrophoresis, Gel, Two-Dimensional, Glyceraldehyde-3-Phosphate Dehydrogenases, Hela Cells, Humans, Immunosuppressive Agents, Kidney, Male, Membrane Potentials, Mitochondria, Liver, Mitochondrial ADP, ATP Translocases, Mitochondrial Membranes, Molecular Sequence Data, Protein Interaction Mapping, Rats, Rats, Wistar, Sequence Homology, Amino Acid, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Subcellular Fractions, Voltage-Dependent Anion Channel 1
Check for Full Text / PubMed Unique Identifier (PMID): 17072346
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