Mitochondrial Dynamics in the Presence of Neurodegenerative Disease
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Mitochondrial dysfunction is an early event in many neurodegenerative diseases, with impaired bioenergetics and migration acting as neurodegenerative triggers. Mitochondrial disruption in the form of reduced bioenergetic capacity, increased oxidative stress and reduced resistance to stress is observed in several disease models. Mitochondria are essential for cellular function due to their role in ATP production, metabolic regulation, cell cycling, signaling pathways, and development. Neurons are responsible for buffering calcium fluxes during synaptic transmission while providing the energy for vesicle release and recycling, maintenance of membrane potential, and axonal and dendritic transport. Maintaining healthy mitochondria is crucial to meet the bioenergetic demands of a neuron and is achieved by maintaining a careful balance between mitochondrial biogenesis, transport, dynamics and mitophagy. In glaucoma, increased intraocular pressure is a stressor for ganglion cells and is implicated in dysfunction of the mitochondrial fusion proteins, Mitofusin 1 and Mitofusin 2, that regulate mitochondrial dynamics and transport. Here we propose that post-translational modifications of mitofusins disrupt mitochondria dynamics and transport. We found impaired mitochondrial dynamics and transport result in the accumulation of Mitofusin 2 in the somas of the retinal ganglion cells, intervening in the dissemination of energy throughout the axons, resulting in the eventual death of the neurons. Based on our findings, we propose a mechanism by which mitochondrial dysfunction is triggered in glaucoma via intraocular pressure through the inactivation of kinases.
- Pathology