Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron deregulation

• Main Authors: Maura Poli, Manuela Derosas, Sara Luscieti, Patrizia Cavadini, Alessandro Campanella, Rosanna Verardi, Dario Finazzi, Paolo Arosio
• Format: Article
• Language: English
• Published: Elsevier 2010-08-01
• Series: Neurobiology of Disease
• Subjects: Pantothenate kinase; Ferroportin; Iron metabolism; Ferritin; Neurodegeneration with brain iron accumulation
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996110001063

Pantothenate kinase 2 (Pank2) is a mitochondrial enzyme that catalyses the first regulatory step of Coenzyme A synthesis and that is responsible for a genetic movement disorder named Pank-associated neurodegeneration (PKAN). This is characterized by abnormal iron accumulation in the brain, particularly in the globus pallidus. We downregulated Pank2 in some cell lines by using specific siRNAs to study its effect on iron homeostasis. In HeLa cells this caused a reduction of cell proliferation and of aconitase activity, signs of cytosolic iron deficiency without mitochondrial iron deposition, and a 12-fold induction of ferroportin mRNA. Pank2 silencing caused a strong induction of ferroportin mRNA also in hepatoma HepG2, a modest one in neuroblastoma SH-SY5Y and none in glioma U373 cells. A reduction of cell growth was observed in all these cell types. The strong Pank2-mediated alteration of ferroportin expression in some cell types might alter iron transfer to the brain and be connected with brain iron accumulation.