Mitochondrial transport in symmetric and asymmetric axons with multiple branching junctions: a computational study

Abstract

Mitochondrial aging has been proposed to be involved in a variety of neurodegenerative disorders, such as Parkinson’s disease. Here, we explore the impact of multiple branching junctions in axons on the mean age of mitochondria and their age density distributions in demand sites. The study examined mitochondrial concentration, mean age, and age density distribution in relation to the distance from the soma. We developed models for a symmetric axon containing 14 demand sites and an asymmetric axon containing 10 demand sites. We investigated how the concentration of mitochondria changes when an axon splits into two branches at the branching junction. Additionally, we studied whether mitochondrial concentrations in the branches are affected by what proportion of mitochondrial flux enters the upper branch versus the lower branch. Furthermore, we explored whether the distributions of mitochondrial mean age and age density in branching axons are affected by how the mitochondrial flux splits at the branching junction. When the mitochondrial flux is unevenly split at the branching junction of an asymmetric axon, with a greater proportion of the flux entering the longer branch, the average age of mitochondria (system age) in the axon increases. Our findings elucidate the effects of axonal branching on the mitochondrial age.

Keywords:

• Neurodegeneration
• mitochondrial aging
• Parkinson’s disease
• large axonal arbors
• computational biology

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

IAK acknowledges the fellowship support of the Paul and Daisy Soros Fellowship for New Americans and the NIH/National Institute of Mental Health (NIMH) Ruth L. Kirchstein NRSA (F30 MH122076-01). AVK acknowledges the support of the National Science Foundation (award CBET-2042834) and the Alexander von Humboldt Foundation through the Humboldt Research Award.