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) |
|---|---|
| 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 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Regulation of 2-oxoglutarate (α-ketoglutarate) dehydrogenase stability by the RING finger ubiquitin ligase siah. / Habelhah, Hasem; Laine, Aaron; Erdjument-Bromage, Hediye; Tempst, Paul; Gershwin, M. Eric; Bowtell, David D L; Ronai, Ze'ev.
In: Journal of Biological Chemistry, Vol. 279, No. 51, 17.12.2004, p. 53782-53788.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of 2-oxoglutarate (α-ketoglutarate) dehydrogenase stability by the RING finger ubiquitin ligase siah
AU - Habelhah, Hasem
AU - Laine, Aaron
AU - Erdjument-Bromage, Hediye
AU - Tempst, Paul
AU - Gershwin, M. Eric
AU - Bowtell, David D L
AU - Ronai, Ze'ev
PY - 2004/12/17
Y1 - 2004/12/17
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=11144241609&partnerID=8YFLogxK
U2 - 10.1074/jbc.M410315200
DO - 10.1074/jbc.M410315200
M3 - Article
C2 - 15466852
AN - SCOPUS:11144241609
VL - 279
SP - 53782
EP - 53788
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 51
ER -