Cellular and Molecular Consequences of Respiratory Chain Defects in Neurons

Project: Research project

Project Details

Description

Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been associated with various primary mitochondrial diseases as well as with neurodegenerative disorders. Such disorders can be caused by defects in nuclear or mitochondrial DNA (mtDNA). We propose to take advantage of existing and new mouse models created in our lab to manipulate the mtDNA to study fundamental mechanisms of the role of mtDNA mutations in neurodegeneration. We will also use DNA editing enzymes to further modulate mtDNA heteroplasmy in vivo. We will analyze the ability of different neuronal types (glutamatergic and dopaminergic) to accumulate mtDNA deletions (aim#1) and a pathogenic point mutation in a tRNA gene (aim#2). With these models in place, we will also study the susceptibility of glutamatergic and dopaminergic neuronal subtypes to OXPHOS defects.
StatusActive
Effective start/end date5/15/123/31/22

Funding

  • National Institute of Neurological Disorders and Stroke: $361,826.00
  • National Institute of Neurological Disorders and Stroke: $386,640.00
  • National Institute of Neurological Disorders and Stroke: $334,688.00
  • National Institute of Neurological Disorders and Stroke: $322,974.00
  • National Institute of Neurological Disorders and Stroke: $445,161.00
  • National Institute of Neurological Disorders and Stroke: $36,682.00
  • National Institute of Neurological Disorders and Stroke: $57,389.00
  • National Institute of Neurological Disorders and Stroke: $386,640.00
  • National Institute of Neurological Disorders and Stroke: $331,341.00

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