iPSC-derived neuronal models of PANK2-associated neurodegeneration reveal mitochondrial dysfunction contributing to early disease
Fig 5
Neuronal response to excess extracellular iron treatment.
A) Schematic representation of the iron handling gene products analyzed in this figure. Transferrin receptor (TFR) binds Transferrin bound extracellular iron and is internalised via endocytosis. Ferritin molecules FTH and FTL bind the cytosolic labile iron pool. Iron import to mitochondria is performed by Mitoferrins (MFRN1 and MFRN2) and excess mitochondrial iron is stored in Mitochondrial Ferritin (FTMT). Neuronal iron export is performed by Ferroportin (FPN). B) Quantitative PCR analysis of iron responsive genes under basal conditions (dark grey bars) and after 18 hours of 50 μM ferric ammonium citrate treatment (light grey bars). C) Western blot analysis of iron responsive proteins TFR and FTH. D) Densitometry analysis of the western blots in C). Patient 1 = 2 clones, patient 2 = 2 clones, patient 3 = 2 clones. C-D) Patient 1 = 1 clone, patient 2 = 1 clone, patient 3 = 1 clone. *p<0.05, **p<0.01. Numbers in histograms represent experimental replicates, and n = 4 throughout B).