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Iron alters cell survival in a mitochondria-dependent pathway in ovarian cancer cells.
Biochemical Journal (2015)
  • Edward Haller, University of South Florida

ABSTRACT The role of iron in the development of cancer remains unclear. We previously reported that iron reduces cell survival in a Ras/mitogen-activated protein kinase (MAPK)-dependent manner in ovarian cells; however, the underlying downstream pathway leading to reduced survival was unclear. Although levels of intracellular iron, ferritin/CD71 protein and reactive oxygen species did not correlate with iron-induced cell survival changes, we identified mitochondrial damage (via TEM) and reduced expression of outer mitochondrial membrane proteins (translocase of outer membrane: TOM20 and TOM70) in cell lines sensitive to iron. Interestingly, Ru360 (an inhibitor of the mitochondrial calcium uniporter) reversed mitochondrial changes and restored cell survival in HEY ovarian carcinoma cells treated with iron. Further, cells treated with Ru360 and iron also had reduced autophagic punctae with increased lysosomal numbers, implying cross-talk between these compartments. Mitochondrial changes were dependent on activation of the Ras/MAPK pathway since treatment with a MAPK inhibitor restored expression of TOM20/TOM70 proteins. Although glutathione antioxidant levels were reduced in HEY treated with iron, extracellular glutamate levels were unaltered. Strikingly, oxalomalate (inhibitor of aconitase, involved in glutamate production) reversed iron-induced responses in a similar manner to Ru360. Collectively, our results implicate iron in modulating cell survival in a mitochondria-dependent manner in ovarian cancer cells.

  • Mitochondria,
  • mitophagy,
  • ROS,
  • intracellular iron,
  • cell survival,
  • MAPK
Publication Date
February 1, 2015
Publisher Statement
© 2015 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)( which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
Citation Information
Edward Haller. "Iron alters cell survival in a mitochondria-dependent pathway in ovarian cancer cells." Biochemical Journal Vol. 466 Iss. 2 (2015)
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