Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload

Xueshan Gao, Mingwei Qian, Jian Li Campian, James Marshall, Zhanxiang Zhou, Andrew M. Roberts, Yujian Kang, Sumanth D. Prabhu, Xiao Feng Sun, John W. Eaton

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

In patients with hemochromatosis, cardiac dysfunction may appear years after they have reached a state of iron overload. We hypothesized that cumulative iron-catalyzed oxidant damage to mitochondrial DNA (mtDNA) might explain the cardiomyopathy of chronic iron overload. Mice were given repetitive injections of iron dextran for a total of 4. weeks after which the iron-loaded mice had elevated cardiac iron, modest cardiac hypertrophy, and cardiac dysfunction. qPCR amplification of near-full-length (~. 16. kb) mtDNA revealed >. 50% loss of full-length product, whereas amounts of a qPCR product of a nuclear gene (13. kb region of beta globin) were unaffected. Quantitative rtPCR analyses revealed 60-70% loss of mRNA for proteins encoded by mtDNA with no change in mRNA abundance for nuclear-encoded respiratory subunits. These changes coincided with proportionate reductions in complex I and IV activities and decreased respiration of isolated cardiac mitochondria. We conclude that chronic iron overload leads to cumulative iron-mediated damage to mtDNA and impaired synthesis of mitochondrial respiratory chain subunits. The resulting respiratory dysfunction may explain the slow development of cardiomyopathy in chronic iron overload and similar accumulation of damage to mtDNA may also explain the mitochondrial dysfunction observed in slowly progressing diseases such as neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)401-407
Number of pages7
JournalFree Radical Biology and Medicine
Volume49
Issue number3
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

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Iron Overload
Cardiomyopathies
Mitochondrial DNA
Iron
Messenger RNA
beta-Globins
Hemochromatosis
Cardiomegaly
Electron Transport
Dextrans
Oxidants
Neurodegenerative Diseases
Mitochondria
Respiration
Injections
Amplification
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Gao, X., Qian, M., Campian, J. L., Marshall, J., Zhou, Z., Roberts, A. M., ... Eaton, J. W. (2010). Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload. Free Radical Biology and Medicine, 49(3), 401-407. https://doi.org/10.1016/j.freeradbiomed.2010.04.033

Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload. / Gao, Xueshan; Qian, Mingwei; Campian, Jian Li; Marshall, James; Zhou, Zhanxiang; Roberts, Andrew M.; Kang, Yujian; Prabhu, Sumanth D.; Sun, Xiao Feng; Eaton, John W.

In: Free Radical Biology and Medicine, Vol. 49, No. 3, 01.08.2010, p. 401-407.

Research output: Contribution to journalArticle

Gao, X, Qian, M, Campian, JL, Marshall, J, Zhou, Z, Roberts, AM, Kang, Y, Prabhu, SD, Sun, XF & Eaton, JW 2010, 'Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload', Free Radical Biology and Medicine, vol. 49, no. 3, pp. 401-407. https://doi.org/10.1016/j.freeradbiomed.2010.04.033
Gao, Xueshan ; Qian, Mingwei ; Campian, Jian Li ; Marshall, James ; Zhou, Zhanxiang ; Roberts, Andrew M. ; Kang, Yujian ; Prabhu, Sumanth D. ; Sun, Xiao Feng ; Eaton, John W. / Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload. In: Free Radical Biology and Medicine. 2010 ; Vol. 49, No. 3. pp. 401-407.
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