Mitochondrial dysfunction as a trigger of programmed axon death

Mitochondrial failure has long been associated with programmed axon death (Wallerian degeneration, WD), a widespread and potentially preventable mecha-nism of axon degeneration. While early findings in axotomised axons indicated that mitochondria are involved during the execution steps of this pathway, recent studies suggest that in addition, mitochondrial dysfunction can initiate programmed axon death without physical injury. As mitochondrial dysfunction is associated with disorders involving early axon loss, including Parkinson's disease, peripheral neuropathies, and multiple sclerosis, the findings that programmed axon death is activated by mitochondrial impairment could indicate the involvement of druggable mechanisms whose disruption may protect axons in such diseases. Here, we review the latest developments linking mitochondrial dysfunction to programmed axon death and discuss their implications for injury and disease.

Automated summary

Recent studies have shown that mitochondrial dysfunction plays a role in programmed axon death, not only in the execution steps of this pathway but also potentially initiating axon death without physical injury. This could indicate druggable mechanisms for protecting axons in diseases like Parkinson's disease, peripheral neuropathies, and multiple sclerosis.