Dopamine‑iron homeostasis interaction rescues mitochondrial fitness in Parkinson's disease

• DOI: 10.1016/j.nbd.2024.106506
• Publication Date: 2024-04-21T05:09:32Z
• Authors: Chiara Buoso; Markus Seifert; Martin Lang; Corey M. Griffith; Begoña Talavera A...; Maria Paulina Cas...; Christine Fischer; Carolina Doerrier; Heribert Talasz; Alessandra Zanon; Peter P. Pramstaller; Emma L. Schymanski; Irene Pichler; Guenter Weiss
• Keywords: Ferroportin; Transferrin receptor

Imbalances of iron and dopamine metabolism along with mitochondrial dysfunction have been linked to the pathogenesis Parkinson's disease (PD). We previously suggested a direct link between homeostasis metabolism, as can increase cellular uptake into macrophages thereby promoting oxidative stress responses. In this study, we investigated interplay iron, dopamine, activity in neuroblastoma SH-SY5Y cells human induced pluripotent stem cell (hiPSC)-derived dopaminergic neurons differentiated from healthy control PD patient mutation α-synuclein (SNCA) gene. cells, treatment resulted increased expression transmembrane transporters transferrin receptor 1 (TFR1), ferroportin (FPN), mitoferrin2 (MFRN2) intracellular accumulation, suggesting that may promote uptake. Furthermore, supplementation led reduced fitness including decreased respiration, cytochrome c efficiency, mtDNA copy number citrate synthase activity, impaired aconitase activity. derived individual, showed comparable effects observed cells. The hiPSC-derived harboring an endogenous SNCA demonstrated altered homeostasis, capacity alterations tricarboxylic acid cycle metabolic pathways compared neurons. Importantly, promoted rescue effect by increasing activating antioxidant response, normalizing metabolite levels function. These observations provide evidence affects responses function while restore disturbed regulatory network