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Updated: Jun 13, 2026

Quantification of Coenzyme A in Cells and Tissues
Published on: September 27, 2019
Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron
Maura Poli1, Manuela Derosas, Sara Luscieti
1Dipartimento Materno Infantile e Tecnologie Biomediche, Università di Brescia, viale Europa 11, 25123 Brescia, Italy.
Abstract:
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.
Insights
Pantothenate kinase 2 (Pank2) downregulation causes cellular iron dysregulation and reduced growth. This Pank2 silencing significantly impacts ferroportin mRNA levels, potentially affecting brain iron accumulation in neurodegenerative diseases like PKAN.
Area of Science:
- Biochemistry
- Neuroscience
- Cell Biology
Background:
- Pantothenate kinase 2 (Pank2) is a mitochondrial enzyme crucial for Coenzyme A synthesis.
- Pank2 dysfunction causes PKAN, a neurodegenerative disorder marked by brain iron accumulation, especially in the globus pallidus.
Purpose of the Study:
- To investigate the impact of Pank2 downregulation on cellular iron homeostasis.
- To explore the relationship between Pank2, ferroportin expression, and iron metabolism.
Main Methods:
- Pank2 was downregulated in various cell lines (HeLa, HepG2, SH-SY5Y, U373) using small interfering RNAs (siRNAs).
- Cell proliferation, aconitase activity, and ferroportin mRNA levels were analyzed.
Main Results:
- Pank2 silencing in HeLa cells led to reduced proliferation, decreased aconitase activity, and a 12-fold increase in ferroportin mRNA.
- Significant ferroportin mRNA induction was observed in HepG2 and SH-SY5Y cells, but not in U373 cells.
- Reduced cell growth was a common outcome across all tested cell types.
Conclusions:
- Pank2 downregulation significantly alters ferroportin expression in a cell-type-dependent manner.
- These alterations in ferroportin may influence iron transport to the brain, potentially contributing to iron accumulation in PKAN.
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