Regulation of 2-oxoglutarate (α-ketoglutarate) dehydrogenase stability by the RING finger ubiquitin ligase siah Journal Article
| Authors: | Habelhah, H.; Laine, A.; Erdjument-Bromage, H.; Tempst, P.; Gershwin, M. E.; Bowtell, D. D. L.; Ronai, Z. |
| Article Title: | Regulation of 2-oxoglutarate (α-ketoglutarate) dehydrogenase stability by the RING finger ubiquitin ligase siah |
| Abstract: | The 2-oxoglutarate dehydrogenase complex (OGHDC) (also known as the α-ketoglutarate dehydrogenase complex) is a rate-limiting enzyme in the mitochondrial Krebs cycle. Here we report that the RING finger ubiquitin-protein isopeptide ligase Siah2 binds to and targets OGDHC-E2 for ubiquitination- dependent degradation. OGDHC-E2 expression and activity are elevated in Siah2-/- cells compared with Siah2+/+ cells. Deletion of the mitochondrial targeting sequence of OGDHC-E2 results in its cytoplasmic localization and rapid proteasome-dependent degradation in Siah2+/+ but not in Siah2-/- cells. Significantly, because of its overexpression or disruption of the mitochondrial membrane potential, the release of OGDHC-E2 from mitochondria to the cytoplasm also results in its concomitant degradation. The role of the Siah family of ligases in the regulation of OGDHC-E2 stability is expected to take place under pathological conditions in which the levels of OGDHC-E2 are altered. |
| Keywords: | controlled study; protein expression; human cell; gene deletion; ubiquitin; protein localization; animals; mice; gene overexpression; proteasome; proteasome endopeptidase complex; ubiquitin protein ligase; enzyme degradation; protein targeting; cell line; protein binding; protein stability; pathology; enzyme activity; hela cells; transfection; transcription factors; nuclear proteins; blotting, western; enzyme regulation; ubiquitination; kinetics; cell culture; gene disruption; immunoprecipitation; cytoplasm; plasmids; microscopy, fluorescence; protein structure, tertiary; enzyme kinetics; enzyme binding; mitochondria; ubiquitin-protein ligases; mitochondrion; transgenes; knockout gene; electrophoresis, polyacrylamide gel; enzyme stability; membrane potentials; biological membranes; cytoplasmic localization; mitochondrial krebs cycle; oxoglutarate dehydrogenase; ketoglutarate dehydrogenase complex; humans; human; priority journal; article; 2-oxoglutarate dehydrogenase complex (oghdc) |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 279 |
| Issue: | 51 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2004-12-17 |
| Start Page: | 53782 |
| End Page: | 53788 |
| Language: | English |
| DOI: | 10.1074/jbc.M410315200 |
| PROVIDER: | scopus |
| PUBMED: | 15466852 |
| DOI/URL: | |
| Notes: | J. Biol. Chem. -- Cited By (since 1996):28 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Source: Scopus |
