Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.9.3.1 (
cytochrome oxidase
)
8,822
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Elevated mitochondrial O-GlcNAcylation caused by hyperglycemia, as occurs in diabetes, significantly contributes to mitochondrial dysfunction and to diabetic cardiomyopathy. However, little is known about the enzymology of mitochondrial O-GlcNAcylation. Herein, we investigated the enzymes responsible for cycling O-GlcNAc on mitochondrial proteins and studied the mitochondrial transport of UDP-GlcNAc. Analyses of purified rat heart mitochondria from normal and streptozocin-treated diabetic rats show increased mitochondrial
O-GlcNAc transferase
(
OGT
) and a concomitant decrease in the mito-specific O-GlcNAcase (OGA). Strikingly,
OGT
is mislocalized in cardiac mitochondria from diabetic rats. Interaction of
OGT
and
complex IV
observed in normal rat heart mitochondria is visibly reduced in diabetic samples, where
OGT
is mislocalized to the matrix. Live cell OGA activity assays establish the presence of O-GlcNAcase within the mitochondria. Furthermore, we establish that the inner mitochondrial membrane transporter, pyrimidine nucleotide carrier, transports UDP-GlcNAc from the cytosol to the inside of the mitochondria. Knockdown of this transporter substantially lowers mitochondrial O-GlcNAcylation. Inhibition of
OGT
or OGA activity within neonatal rat cardiomyocytes significantly affects energy production, mitochondrial membrane potential, and mitochondrial oxygen consumption. These data suggest that cardiac mitochondria not only have robust O-GlcNAc cycling, but also that dysregulation of O-GlcNAcylation likely plays a key role in mitochondrial dysfunction associated with diabetes.
...
PMID:Diabetes-associated dysregulation of O-GlcNAcylation in rat cardiac mitochondria. 2591 8
