Regulation of mitochondrial aconitase by phosphorylation in diabetic rat heart

Mitochondrial dysfunction and protein kinase C (PKC) activation are consistently found in diabetic cardiomyopathy but their relationship remains unclear. This study identified mitochondrial aconitase as a downstream target of PKC activation using immunoblotting and mass spectrometry, and then charac...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2009-03, Vol.66 (5), p.919-932
Main Authors: Lin, G, Brownsey, R. W, MacLeod, K. M
Format: Article
Language:English
Subjects:
Aconitase 2
Aconitate Hydratase - chemistry
Aconitate Hydratase - genetics
Aconitate Hydratase - metabolism
Amino Acid Sequence
Animals
ATP Citrate (pro-S)-Lyase - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Citric Acid Cycle - physiology
Diabetes
Diabetes Mellitus, Experimental - metabolism
Enzyme Activation
Heart
Humans
Immunohistochemistry
Isoenzymes - metabolism
Life Sciences
Mass spectrometry
Mitochondria - enzymology
Mitochondria - ultrastructure
Models, Molecular
Molecular biology
Molecular Sequence Data
Myocardium - cytology
Myocardium - enzymology
Phosphorylation
PKC
Protein Kinase C - metabolism
Protein Structure, Tertiary
Proteins
Rats
Rats, Wistar
Research Article
Rodents
Signal Transduction - physiology
Studies
TCA cycle
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Summary:Mitochondrial dysfunction and protein kinase C (PKC) activation are consistently found in diabetic cardiomyopathy but their relationship remains unclear. This study identified mitochondrial aconitase as a downstream target of PKC activation using immunoblotting and mass spectrometry, and then characterized phosphorylation-induced changes in its activity in hearts from type 1 diabetic rats. PKCβ₂ co-immunoprecipitated with phosphorylated aconitase from mitochondria isolated from diabetic hearts. Augmented phosphorylation of mitochondrial aconitase in diabetic hearts was found to be associated with an increase in its reverse activity (isocitrate to aconitate), while the rate of the forward activity was unchanged. Similar results were obtained on phosphorylation of mitochondrial aconitase by PKCβ₂ in vitro. These results demonstrate the regulation of mitochondrial aconitase activity by PKC-dependent phosphorylation. This may influence the activity of the tricarboxylic acid cycle, and contribute to impaired mitochondrial function and energy metabolism in diabetic hearts.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-009-8696-3