Analysis of mitochondrial transport dynamics in axons

Abstract

The polarized structure and extremely long neurites pose a unique challenge for neurons to distribute mitochondria to the appropriate locations. Hence, proper transport of mitochondria to the appropriate locations is especially important for neuronal functions. Consequently, defective mitochondrial transport can have deleterious effects on neuronal functions and survival. It is widely accepted that mitochondria move from the cell body to axon terminals and vice versa. Although mitochondria are known to move bi-directionally from the cell body to axon terminals and vice versa, the dynamic pattern of mitochondrial transport in the entire length of axons for an extended period of time have not been thoroughly examined. Using the photo-switchable fluorescent protein dendra-2 targeted to mitochondria, we tracked individual mitochondria in the whole axon. Surprisingly, we find mitochondria that originated from the axon terminals traveling in the retrograde direction never reach at the cell body. Retrogradely moving mitochondria failed to enter the cell body due to fusion to existing mitochondria or pausing in the middle of axons, while anterogradely moving mitochondria reach the axon terminals with less interruption. In addition, the speed of mitochondrial transport varies along regions with different densities of stationary mitochondria. Stationary mitochondria were present at higher density in axon proximal to the cell body, although inter-mitochondrial spacing is random following Gumble-like distribution. Furthermore, we derived a mathematical model using the Fokker- Planck equation to characterize the features of mitochondria movement, which was successfully adopted to determine altered mitochondrial transport in axons overexpressing parkin. Our analysis and model provide new insights into the dynamics of mitochondria transport in axons of normal or unhealthy neurons.