Neurons are highly energy-demanding cells, and their viability and functions rely heavily on proper mitochondrial function. Mitochondria functions include the regulation of calcium (Ca2+) homeostasis, ATP synthesis, apoptotic cell death, and reactive oxygen species (ROS) production. Given that mitochondria play various crucial roles in neurons and thus proper quality control of mitochondria is essential, removal of dysfunctional mitochondria, a process referred to as mitophagy, is critical to ensure maintenance of sufficient pools of healthy neuronal mitochondria. However, it remains an open question how dysfunctional mitochondria are effectively removed from long neuronal processes such as axons, far from the cell body, where many neuronal mitochondria reside. In this dissertation, I primarily focus on understanding how damaged mitochondria are eliminated from the long axons of neurons such as retinal ganglion cells (RGCs). I perturbed the mitophagy receptor Optineurin (OPTN) to determine how that affects mitochondria degradation within Xenopus laevis RGC axons. Live-imaging of the optic nerve revealed that while normally there is not much mitophagy occurring locally within the axons, expression of disease-associated versions of OPTN increases the local degradation of axonal mitochondria. Most importantly, whenever there is local axonal degradation of mitochondria, this is accomplished by unusual mitochondria shedding process that the Marsh-Armstrong lab had previously described, referred to as transmitophagy. This supports the view that under healthy conditions there is a low baseline of mitophagy within axons, but that mutations in mitophagy machinery result in large increases in the local degradation of axonal mitochondria. Most notably, however, under both the baseline and perturbed conditions a significant number of axonal mitochondria are degraded outside of the axons.The second part of the dissertation shows that β-amyloid peptides (Aβ), a key molecule in Alzheimer’s disease (AD) pathology where Aβ are accumulating within neuronal mitochondria and leading to dysregulated mitochondrial functions, move together with the mitochondria in RGC axons, and, in particular, a large amount of Aβ and mitochondria were stopped in the axons and some of them appeared to be outside the optic nerve similar to what was shown in glaucoma-associated E50K OPTN mutant, suggesting transmitophagy process. Overall, my work contributes to our understanding of how mitochondria debris and toxic peptides are cleared from the vertebrate nervous system. Besides advancing basic understanding of these processes, my work also may point the way towards therapeutic strategies for neurodegenerative diseases, for example, accelerating clearance of damaged mitochondria and Aβ through transmitophagy.