In our latest study, just published in Neurobiology of Disease Elsevier, we investigated the interaction between iron and dopamine metabolism and mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD).

In the study, we used neuroblastoma cells (SH-SY5Y) and dopaminergic neurons derived from induced pluripotent stem cells (iPSCs) of a control and a PD patient with an α-synuclein (SNCA) gene mutation.

In SH-SY5Y cells, dopamine increased the expression of iron transporters and caused iron accumulation, suggesting that dopamine alters iron homeostasis in neuronal cells. This led to impaired mitochondrial function, evidenced by reduced respiration, mtDNA copy number, and citrate synthase activity, as well as increased oxidative stress.

Similarly, in neurons from a healthy control, dopamine reduced mitochondrial fitness. However, in PD neurons with the SNCA mutation, dopamine promoted mitochondrial respiration, activated antioxidant responses, and normalized metabolite levels associated with mitochondrial function by shuttling iron between cytoplasm and mitochondria.

These findings expand our knowledge on the effect of dopaminergic treatment on iron-mitochondria biochemical pathways, highlight the importance of a spatio-temporal distribution of iron and dopamine for brain function and offer new perspectives for targeted treatments to improve altered intracellular iron distribution, protect mitochondria and reduce oxidative stress in PD patients.

Full article here: https://doi.org/10.1016/j.nbd.2024.106506