title: Identification of L-ferritin in neuromelanin granules of the human substantia nigra: a targeted proteomics approach.
abstract: 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.
authors.affiliation: Clinic and Polyclinic for Psychiatry and Psychotherapy, Julius-Maximilians-Universität Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Tribl
authors.forename: Esther
authors.initials: E
authors.lastname: Asan
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Tatschner
authors.forename: Elmar
authors.initials: E
authors.lastname: Langenfeld
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Manfred
authors.initials: M
authors.lastname: Gerlach
authors.forename: Katrin
authors.initials: K
authors.lastname: Marcus