Author Type

Graduate Student

Date of Award

Spring 12-12-2022

Document Type

Thesis

Publication Status

Version of Record

Degree Name

Master of Science (MS)

Department

Biological Sciences

First Advisor

Gregory Macleod

Abstract

Mitochondria are vital organelles essential for proper function of the human body. Mutations in genes encoding mitochondrial proteins lead to mitochondrial dysfunction and severe neurological symptoms. Children reported to have mutations within the gene encoding the enzyme, mitochondrial malate dehydrogenase (MDH2) exhibit symptoms of hypotonia, lactic acidosis and epilepsy. No treatment exists for this disorder and the neurological symptoms stemming from MDH2 mutations require further investigation. Decrease in pH, associated with an increase in lactate production, may contribute to symptoms experienced by children with MDH2 mutations. To investigate pH in individuals with MDH2 mutations, we used CRISPR/Cas9 techniques to introduce mutations into the endogenous locus of MDH2 in Drosophila melanogaster. By using in vivo confocal microscopy, we investigated cytosolic pH and mitochondrial energy metabolism in neurons of larval Drosophila. Results from these experiments may help explain the basis of neurological symptoms and inform therapeutic approaches for children with MDH2 mutations.

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