Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron deregulation.
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.
Poli
Maura
M
Dipartimento Materno Infantile e Tecnologie Biomediche, Università di Brescia, viale Europa 11, 25123 Brescia, Italy.
Derosas
Manuela
M
Luscieti
Sara
S
Cavadini
Patrizia
P
Campanella
Alessandro
A
Verardi
Rosanna
R
Finazzi
Dario
D
Arosio
Paolo
P
D000154:Aconitate Hydratase / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011524:Protoporphyrins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000098742:Ferroportin; D000099156:Superoxide Dismutase 2
D000154:Aconitate Hydratase; D027682:Cation Transport Proteins; D007501:Iron; D017853:Phosphotransferases (Alcohol Group Acceptor); D011524:Protoporphyrins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase; D000098742:Ferroportin; D000099156:Superoxide Dismutase 2; C023088:pantothenate kinase