How does mitochondrial morphology change in neurons with age and disease?

Mitochondria are fundamental to the function of our neurons, and defects in the function of this important organelle are found in several neurodegenerative disorders, as well as in normal ageing. Alterations in the form and morphology of mitochondria have been linked to their function and ability to adapt to dysfunction. However, a detailed study of the 3D morphology of neuronal mitochondria within human neurons has yet to be undertaken.

This project will use innovative 3D electron microscopy to reconstruct the mitochondria in human neurons within populations which are vulnerable in neurodegenerative disease, including from the substantia nigra (Parkinson's) and hippocampus (Alzheimer's). This will enable us to study the morphology of mitochondria at an unprecedented depth, expanding our understanding of how mitochondrial morphology changes in response to mitochondrial dysfunction, neurodegeneration and protein accumulation. Training will be provided in the use of the serial block face scanning electron microscope, sample preparation, histochemistry and immunolabelling, neuroanatomy, bioinformatics and data analysis. Additional training and support for personal and professional development will also be provided through the Newcastle University Researcher Development Programme.

This project will add to our understanding of mitochondrial dysfunction within neurons and characterise important structural changes in neurodegenerative disease. While mitochondrial dynamics have been well defined in many cell models, our understanding of mitochondrial connectivity in neurons and how this changes with ageing and disease is poorly understood. A deeper understanding of these morphological changes will further our understanding of neurodegeneration and inform whether altering mitochondrial morphology is a potential therapeutic target.