A Novel Association Between Glutamine Metabolism and Clinical Progression in DCMA, A Mitochondrial Cardiomyopathy
Date
2020-02-27
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Abstract
The Dilated Cardiomyopathy with Ataxia Syndrome (DCMA) is a severe mitochondrial disorder with a high rate of mortality. DCMA is caused by mutations in the poorly characterized DNAJC19 gene which cause a variety of clinical characteristics including elevated 3-methylglutaconic and 3-methylglutaric acids. How these mutations elicit the complex disease presentation is unclear. For this thesis, I developed a fibroblast-based model to study DCMA mitochondrial metabolism. Using stable isotope labeling and metabolomics, I demonstrate that DCMA may be linked to alterations in glutamine catabolism and propose a new model for DCMA involving an inability to import glutamate into the mitochondria. Furthermore, I show that the metabolic phenotype correlates with patient clinical progression. This novel finding could allow clinicians to predict DCMA patient outcomes. This thesis paves the way to reclassifying DCMA as a disorder of glutamine metabolism, and may guide more effective diagnostics for preventing the early death of affected children.
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Keywords
Metabolism, Mitochondrial Metabolism
Citation
King, M. A. (2020). A Novel Association Between Glutamine Metabolism and Clinical Progression in DCMA, A Mitochondrial Cardiomyopathy (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.