Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria

John Phillips, Collin Farrell, Yongming Wang, Ashwani K. Singal, Karl Anderson, Manisha Balwani, Montgomery Bissell, Herbert Bonkovsky, Toni Seay, Barry Paw, Robert Desnick, Joseph Bloomer

Research output: Contribution to journalArticle

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Abstract

Accumulation of protoporphyrin IX (PPIX) and Zn-PPIX, are the clinical hallmarks of protoporphyria. Phenotypic expression of protoporphyria is due to decreased activity of ferrochelatase (FECH) or to increased activity of aminolevulinic acid synthase (ALAS) in red blood cells. Other genetic defects have been shown to contribute to disease severity including loss of function mutations in the mitochondrial AAA-ATPase, CLPX and mutations in the Iron-responsive element binding protein 2 (IRP2), in mice. It is clear that multiple paths lead to a common phenotype of excess plasma PPIX that causes a phototoxic reaction on sun exposed areas. In this study we examined the association between mitochondrial iron acquisition and utilization with activity of FECH. Our data show that there is a metabolic link between the activity FECH and levels of MFRN1 mRNA. We examined the correlation between FECH activity and MFRN1 mRNA in cell lines established from patients with the classical protoporphyria, porphyria due to defects in ALAS2 mutations. Our data confirm MFRN1 message levels positively correlated with FECH enzymatic activity in all cell types.

Original languageEnglish (US)
JournalMolecular Genetics and Metabolism
DOIs
StateAccepted/In press - Jan 1 2018

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Ferrochelatase
Messenger RNA
Mutation
Iron Regulatory Protein 2
Cells
Porphyrias
Aminolevulinic Acid
Defects
Solar System
Sun
Adenosine Triphosphatases
Blood
Iron
Erythrocytes
Phenotype
Plasmas
Cell Line
protoporphyrin IX

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria. / Phillips, John; Farrell, Collin; Wang, Yongming; Singal, Ashwani K.; Anderson, Karl; Balwani, Manisha; Bissell, Montgomery; Bonkovsky, Herbert; Seay, Toni; Paw, Barry; Desnick, Robert; Bloomer, Joseph.

In: Molecular Genetics and Metabolism, 01.01.2018.

Research output: Contribution to journalArticle

Phillips, John ; Farrell, Collin ; Wang, Yongming ; Singal, Ashwani K. ; Anderson, Karl ; Balwani, Manisha ; Bissell, Montgomery ; Bonkovsky, Herbert ; Seay, Toni ; Paw, Barry ; Desnick, Robert ; Bloomer, Joseph. / Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria. In: Molecular Genetics and Metabolism. 2018.
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abstract = "Accumulation of protoporphyrin IX (PPIX) and Zn-PPIX, are the clinical hallmarks of protoporphyria. Phenotypic expression of protoporphyria is due to decreased activity of ferrochelatase (FECH) or to increased activity of aminolevulinic acid synthase (ALAS) in red blood cells. Other genetic defects have been shown to contribute to disease severity including loss of function mutations in the mitochondrial AAA-ATPase, CLPX and mutations in the Iron-responsive element binding protein 2 (IRP2), in mice. It is clear that multiple paths lead to a common phenotype of excess plasma PPIX that causes a phototoxic reaction on sun exposed areas. In this study we examined the association between mitochondrial iron acquisition and utilization with activity of FECH. Our data show that there is a metabolic link between the activity FECH and levels of MFRN1 mRNA. We examined the correlation between FECH activity and MFRN1 mRNA in cell lines established from patients with the classical protoporphyria, porphyria due to defects in ALAS2 mutations. Our data confirm MFRN1 message levels positively correlated with FECH enzymatic activity in all cell types.",
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AU - Anderson, Karl

AU - Balwani, Manisha

AU - Bissell, Montgomery

AU - Bonkovsky, Herbert

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AU - Desnick, Robert

AU - Bloomer, Joseph

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