Manganese transport via the transferrin mechanism

Thomas E. Gunter, Brent Gerstner, Karlene K. Gunter, Jon Malecki, Robert Gelein, William M. Valentine, Michael Aschner, David I. Yule

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Excessive manganese (Mn) uptake by brain cells, particularly in regions like the basal ganglia, can lead to toxicity. Mn2+ is transported into cells via a number of mechanisms, while Mn3+ is believed to be transported similarly to iron (Fe) via the transferrin (Tf) mechanism. Cellular Mn uptake is therefore determined by the activity of the mechanisms transporting Mn into each type of cell and by the amounts of Mn2+, Mn3+ and their complexes to which these cells are exposed; this complicates understanding the contributions of each transporter to Mn toxicity. While uptake of Fe3+ via the Tf mechanism is well understood, uptake of Mn3+ via this mechanism has not been systematically studied. The stability of the Mn3+Tf complex allowed us to form and purify this complex and label it with a fluorescent (Alexa green) tag. Using purified and labeled Mn3+Tf and biophysical tools, we have developed a novel approach to study Mn3+Tf transport independently of other Mn transport mechanisms. This approach was used to compare the uptake of Mn3+Tf into neuronal cell lines with published descriptions of Fe3+ uptake via the Tf mechanism, and to obtain quantitative information on Mn uptake via the Tf mechanism. Results confirm that in these cell lines significant Mn3+ is transported by the Tf mechanism similarly to Fe3+Tf transport; although Mn3+Tf transport is markedly slower than other Mn transport mechanisms. This novel approach may prove useful for studying Mn toxicity in other systems and cell types.

Original languageEnglish (US)
Pages (from-to)118-127
Number of pages10
Issue number1
StatePublished - Jan 2013
Externally publishedYes


  • Endosomal transport
  • Manganese toxicity
  • Manganese transport
  • Mitochondria
  • Transferrin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology


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