Mitochondrial Dynamics in Health and Disease

The Mitochondrial Neurobiology and Therapeutics Lab at Mayo Clinic studies how mitochondria react to stress associated with the development of neurodegenerative diseases and aging.

Assessment of mitochondrial motility along axons and dendrites and evaluation of mitochondrial fission and fusion in vitro and in vivo helps scientists understand early molecular mechanisms of human conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, metabolic disorders and aging and provide strategies or combinations of strategies for early interventions.

An example of a combinatorial therapeutic approach could include an application of a compound that blocks stress-induced mitochondrial fission and subsequent removal via selective mitochondrial degradation (mitophagy). At the same time, an additional compound could be used to promote mitochondrial biogenesis to replace damaged organelles.

Axonal trafficking of mitochondria in primary neuron from a wild-type mouse

The video above is a visualization of mitochondria in E17 hippocampal neurons. Axonal trafficking of mitochondria is impaired in neurodegenerative diseases and aging. Restoration of axonal trafficking promotes mitochondria distribution within the axons delivering energy to the distal parts, which supports synaptic activity and could preserve memory function.

Visualization was done using a mitochondria-specific dye, tetramethylrhodamine methyl ester (TMRM). Six hundred frames were acquired by imaging the axon every second using an LSM 510 confocal microscope. Imaging focused on the axon, with the cell body located at the top of the image. The resulting video was analyzed using Analyze, a comprehensive multidimensional medical image processing, visualization and analysis software package developed by the Biomedical Imaging Resource Core at Mayo Clinic.

By treating the microscope image sequence as a spatial stack of cross-sectional images, the volume-rendering algorithms in Analyze produced a 3-D digital kymograph, allowing the motion of multiple organelles over a period of time to be visualized in a single, static 2-D image. This final kymograph allows Dr. Trushina's lab to trace each mitochondrion through all 600 frames to generate a final profile of movement.