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Molecular & Cellular Proteomics 8:1832-1838, 2009.
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Identification of L-ferritin in Neuromelanin Granules of the Human Substantia Nigra

A TARGETED PROTEOMICS APPROACH^*

From the ^aClinic and Polyclinic for Psychiatry and Psychotherapy and
^hClinic and Polyclinic for Child and Adolescent Psychiatry and Psychotherapy, Department of Clinical Neurochemistry and "The National Parkinson Foundation Research Laboratories", Miami, Florida, at the Julius-Maximilians-Universität Würzburg, Füchsleinstrasse 15, 97080 Würzburg,
Departments of ^bFunctional Proteomics and
^fMedical Proteomics and Bioanalytics, Medizinisches Proteom-Center, Ruhr-Universität Bochum, Universitätsstrasse 150, 44780 Bochum,
^cInstitute of Anatomy and Cell Biology, Julius-Maximilians-Universität Würzburg, Koellikerstrasse 6, 97970 Würzburg,
^dCentre for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Feodor-Lynen-Strasse 23, 81377 Munich,
^eInstitute of Forensic Medicine, Julius-Maximilians-Universität Würzburg, Versbacher Strasse 3, 97078 Würzburg, and
^gInstitute of Organic Chemistry, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074 Würzburg, Germany

In the pigmented dopaminergic neurons of the human substantia nigra pars compacta the system relevant in iron storage is the polymer neuromelanin (NM). Although in most cells this function is mainly accomplished by ferritin, this protein complex appears not to be expressed in NM-containing neurons. Nevertheless the conceivable presence of iron-storing proteins as part of the NM granules has recently been discussed on the basis of Mössbauer spectroscopy and synchrotron x-ray microspectroscopy. Intriguingly by combining subcellular fractionation of NM granules, peptide sequencing via tandem mass spectrometry, and the additional confirmation by multiple reaction monitoring and immunogold labeling for electron microscopy, L-ferritin could now be unambiguously identified and localized in NM granules for the first time. This finding not only supports direct evidence for a regulatory role of L-ferritin in neuroectodermal cell pigmentation but also integrates a new player within a complicated network governing iron homeostasis in the dopamine neurons of the human substantia nigra. Thus our finding entails far reaching implications especially when considering etiopathogenetic aspects of Parkinson disease.

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