Investigating the Role of msBDNF – TrkB Signaling in the Maintenance of Mitochondrial Populations Through the BNIP3 Mitophagy Pathway

Author

Jack A. Horton, jahortonFollow

Date of Award

7-2025

Degree Type

Thesis

Degree Name

Master of Science

Department

Biology

Program

Biology (MS)

First Advisor/Chairperson

Robert Belton

Abstract

Maintenance of mitochondrial transport and clearance at the pre- and post-synaptic terminal is an essential function of neuromuscular junctions to meet their high energy demands. Damaged or dysfunctional mitochondria can put stress on these synaptic junctions, ultimately leading to the degradation of the synapse and subsequent cell death. Dysfunctional mitochondria are also often present in neuromuscular diseases such as ALS. One possible mechanism by which neurons may eliminate dysfunctional mitochondria is through the muscle-synthesized BDNF (msBDNF) /TrkB-mediated Bcl-2 nineteen-kD interacting protein (BNIP3) mitophagy pathway, although the relationship is not well-defined. BNIP3 localizes to the mitochondria and triggers a loss of membrane potential leading to mitochondrial destruction. Using a murine model, functional and dysfunctional mitochondrial populations were labelled in the gastrocnemius of control, heterozygous and homozygous muscle-synthesized BDNF knockout mice. Injections of the mitochondria-labeling dye MitoTracker were performed on 52-day-old and 87-day-old mice in order to determine if abnormalities in mitochondrial clearance are a cause of the pathophysiology observed in this model, or possibly a byproduct of it. A BNIP3-specific antibody was used to specifically label dysfunctional mitochondria at the post-synapse of these mice. The goal was to assess the relationship between the lack of msBDNF-TrkB signaling in mice and the presence of BNIP3. Finally, BNIP3 expression and the ratio of functional and dysfunctional mitochondria in gastrocnemius muscle of both control and msBDNF knockout mice was measured to determine if there is a relationship between msBDNF expression and the number of dysfunctional mitochondria at the post-synapse of the neuromuscular junction.

Recommended Citation

Horton, Jack A., "Investigating the Role of msBDNF – TrkB Signaling in the Maintenance of Mitochondrial Populations Through the BNIP3 Mitophagy Pathway" (2025). All NMU Master's Theses. 897.
https://commons.nmu.edu/theses/897

Access Type

Open Access