Accumulation of oxidative DNA damage in brain mitochondria in mouse model of hereditary ferritinopathy

Xiaoling Deng, Ruben Vidal, Ella W. Englander

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Tissue iron content is strictly regulated to concomitantly satisfy specialized metabolic requirements and avoid toxicity. Ferritin, a multi-subunit iron storage protein, is central to maintenance of iron homeostasis in the brain. Mutations in the ferritin light chain (FTL)-encoding gene underlie the autosomal dominant, neurodegenerative disease, neuroferritinopathy/hereditary ferritinopathy (HF). HF is characterized by progressive accumulation of ferritin and iron. To gain insight into mechanisms by which FTL mutations promote neurodegeneration, a transgenic mouse, expressing human mutant form of FTL, was recently generated. The FTL mouse exhibits buildup of iron in the brain and presents manifestations of oxidative stress reminiscent of the human disease. Here, we asked whether oxidative DNA damage accumulates in the FTL mouse brain. Long-range PCR (L-PCR) amplification-mediated DNA damage detection assays revealed that the integrity of mitochondrial DNA (mtDNA) in the brain was significantly compromised in the 12- but not 6-month-old FTL mice. Furthermore, L-PCR employed in conjunction with DNA modifying enzymes, which target specific DNA adducts, revealed the types of oxidative adducts accumulating in mtDNA in the FTL brain. Consistently with DNA damage predicted to form under conditions of excessive oxidative stress, detected adducts include, oxidized guanines, abasic sites and strand breaks. Elevated mtDNA damage may impair mitochondrial function and brain energetics and in the long term contribute to neuronal loss and exacerbate neurodegeneration in HF.

Original languageEnglish (US)
Pages (from-to)44-48
Number of pages5
JournalNeuroscience Letters
Issue number1
StatePublished - Jul 2010


  • Brain
  • DNA damage
  • Ferritin
  • Hereditary ferritinopathy
  • Iron overload
  • Mitochondria

ASJC Scopus subject areas

  • General Neuroscience


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