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.
Original language | English (US) |
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Pages (from-to) | 53782-53788 |
Number of pages | 7 |
Journal | Journal of Biological Chemistry |
Volume | 279 |
Issue number | 51 |
DOIs | |
State | Published - Dec 17 2004 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry