Subcellular proteomics reveals neuromelanin granules to be a lysosome-related organelle

Abstract

The powerful combination of subcellular fractionation and protein identification by electrospray ionization tandem mass spectrometry (ESI-MS/MS) pioneered the molecular elucidation of neuromelanin (NM) granules. We recently isolated NM granules from the human brain and succeeded in the establishment of the first protein profile of this compartment. NM granules are pigmented organelles, which are mainly found in the catecholaminergic neurons of the human substantia nigra (SN) pars compacta and the locus coeruleus. These granules contain the insoluble pigment NM, which is regarded as the most important iron storage system in these neurons. A global examination of NM granules, however, has so far been hampered due to the lack of a pigmented brain stem in rodents, the absence of an appropriate experimental system and their scarcity in the human brain. ‘Subcellular proteomics’, which increasingly emerges as the method of choice to characterize cellular compartments and to elucidate their biogenesis, has recently been shown to be an adequate approach to tackle a thorough description of NM granules. Thereby, NM granules could be described as a ‘lysosome-related organelle’. This indicates a genetic program underlying a biogenesis of NM rather than its autoxidative formation.