Transporting mitochondria in neurons

Abstract

Neurons demand vast and vacillating supplies of energy. As the key contributors of this energy, as well as primary pools of calcium and signaling molecules, mitochondria must be where the neuron needs them, when the neuron needs them. The unique architecture and length of neurons, however, make them a complex system for mitochondria to navigate. To add to this difficulty, mitochondria are synthesized mainly in the soma, but must be transported as far as the distant terminals of the neuron. Similarly, damaged mitochondria—which can cause oxidative stress to the neuron—must fuse with healthy mitochondria to repair the damage, return all the way back to the soma for disposal, or be eliminated at the terminals. Increasing evidence suggests that the improper distribution of mitochondria in neurons can lead to neurodegenerative and neuropsychiatric disorders. Here, we will discuss the machinery and regulatory systems used to properly distribute mitochondria in neurons, and how this knowledge has been leveraged to better understand neurological dysfunction.

The role of mitochondria in axon development and regeneration

“…In cultured rat hippocampal neurons, TRAK1 mediates mitochondrial transport into axons and is preferentially targeted to axons (Van Spronsen et al, ; Loss and Stephenson, ). However, evidence for additional kinesins and potential adaptors or regulators has also emerged, but these are less understood in neurons (Course and Wang, ). The dynein/dynactin complex can also bind the Miro/TRACK complex (Van Spronsen et al, ) (Fig.…”

Mitochondrial transport serves as a mitochondrial quality control strategy in axons: Implications for central nervous system disorders

“…Besides these achievements, insights gained in recent years have revealed the critical contribution of mitochondria to neuronal health . Mitochondria not only serve as the “powerhouse” of neurons but also play essential roles in metabolizing neurotransmitters, buffering Ca 2+ , and sending signal deciding neuronal survival . Mitochondrial quality is therefore the basis of neural homeostasis.…”

“…Their long, thin axons are not only unique in morphology but also fundamental to neuronal functions by forming specialized compartments such as synapses and nodes of Ranvier. To meet the ever‐changing demands of neurons, mitochondria have been located in these distal compartments in axons . However, it is more challenging for neurons to control the quality of these distal mitochondria due to the limited extent of both mitochondrial biogenesis and degradation in axons .…”

“…Specifically, mitochondria newly generated in soma are distributed to axons by anterograde transport, while senescent or damaged mitochondria in axons undergo retrograde transport for repair or autophagic clearance . Mitochondria are distributed according to their quality, which is fundamental to neuronal homeostasis and functions . The alternation of axonal mitochondrial transport is intimately related to compromised mitochondrial quality and thus contributes to neurological disorders.…”

“…3 Mitochondria not only serve as the "powerhouse" of neurons but also play essential roles in metabolizing neurotransmitters, buffering Ca 2+ , and sending signal deciding neuronal survival. 4 Mitochondrial quality is therefore the basis of neural homeostasis. Stress-induced mitochondrial damage results in the collapse of bioenergy generation and even worse, neuronal demise.…”