Journal article
Regulation of 2-Oxoglutarate (α-Ketoglutarate) Dehydrogenase Stability by the RING Finger Ubiquitin Ligase Siah
The Journal of biological chemistry, Vol.279(51), pp.53782-53788
12/17/2004
DOI: 10.1074/jbc.M410315200
PMID: 15466852
Abstract
The 2-oxoglutarate dehydrogenase complex (OGHDC) (also known as the alpha-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.
Details
- Title: Subtitle
- Regulation of 2-Oxoglutarate (α-Ketoglutarate) Dehydrogenase Stability by the RING Finger Ubiquitin Ligase Siah
- Creators
- Hasem HabelhahAaron LaineHediye Erdjument-BromagePaul TempstM. Eric GershwinDavid D. L BowtellZe'ev Ronai
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.279(51), pp.53782-53788
- DOI
- 10.1074/jbc.M410315200
- PMID
- 15466852
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 12/17/2004
- Academic Unit
- Pathology
- Record Identifier
- 9984047860702771
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