Mitochondrial Trafficking on Axons as a Function of Substrate Stiffness

Abstract

Mitochondria are the energy machinery necessary for the maintenance of axonal growth, calcium management and other neuronal functions and disruption of their transport results in neurological disease. Due to the length of neurite extensions, mitochondria travel along microtubules and actin filaments to reach different places along the axon; thus, their transport and density is regulated by the activity of axonal zones and growth cones. Mitochondrial trafficking has been linked to axonal growth and thus is an important property in the study of neuroregeneration. It has previously been shown that axonal growth depends on substrate stiffness, suggesting that the mechanical properties of the substrate might play an important role in axonal transport. In this work we analyzed the transport of mitochondria along the axon as well as the distribution in the growth cone as a function of substrate stiffness, by imaging axonal transport of mitochondria in vitro on cultured rodent DRGs. These results provide insight into the transport mechanisms along the axon as a function of substrate stiffness. Furthermore, these results deepen our knowledge of the effects of mechanical properties of the substrate on the activity of axons and growth cones and show that mitochondrial trafficking may play a role in these effects.