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Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease

During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson’s disease. We have investigated protein and lipid systems involved in the formation of these organelles and...

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Autores principales: Zucca, Fabio A., Vanna, Renzo, Cupaioli, Francesca A., Bellei, Chiara, De Palma, Antonella, Di Silvestre, Dario, Mauri, Pierluigi, Grassi, Sara, Prinetti, Alessandro, Casella, Luigi, Sulzer, David, Zecca, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988730/
https://www.ncbi.nlm.nih.gov/pubmed/29900402
http://dx.doi.org/10.1038/s41531-018-0050-8
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author Zucca, Fabio A.
Vanna, Renzo
Cupaioli, Francesca A.
Bellei, Chiara
De Palma, Antonella
Di Silvestre, Dario
Mauri, Pierluigi
Grassi, Sara
Prinetti, Alessandro
Casella, Luigi
Sulzer, David
Zecca, Luigi
author_facet Zucca, Fabio A.
Vanna, Renzo
Cupaioli, Francesca A.
Bellei, Chiara
De Palma, Antonella
Di Silvestre, Dario
Mauri, Pierluigi
Grassi, Sara
Prinetti, Alessandro
Casella, Luigi
Sulzer, David
Zecca, Luigi
author_sort Zucca, Fabio A.
collection PubMed
description During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson’s disease. We have investigated protein and lipid systems involved in the formation of these organelles and in the synthesis of the neuromelanin of human substantia nigra. Membrane and matrix proteins characteristic of lysosomes were found in neuromelanin-containing organelles at a lower number than in typical lysosomes, indicating a reduced enzymatic activity and likely impaired capacity for lysosomal and autophagosomal fusion. The presence of proteins involved in lipid transport may explain the accumulation of lipid bodies in the organelle and the lipid component in neuromelanin structure. The major lipids observed in lipid bodies of the organelle are dolichols with lower amounts of other lipids. Proteins of aggregation and degradation pathways were present, suggesting a role for accumulation by this organelle when the ubiquitin-proteasome system is inadequate. The presence of proteins associated with aging and storage diseases may reflect impaired autophagic degradation or impaired function of lysosomal enzymes. The identification of typical autophagy proteins and double membranes demonstrates the organelle’s autophagic nature and indicates that it has engulfed neuromelanin precursors from the cytosol. Based on these data, it appears that the neuromelanin-containing organelle has a very slow turnover during the life of a neuron and represents an intracellular compartment of final destination for numerous molecules not degraded by other systems.
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spelling pubmed-59887302018-06-13 Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease Zucca, Fabio A. Vanna, Renzo Cupaioli, Francesca A. Bellei, Chiara De Palma, Antonella Di Silvestre, Dario Mauri, Pierluigi Grassi, Sara Prinetti, Alessandro Casella, Luigi Sulzer, David Zecca, Luigi NPJ Parkinsons Dis Article During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson’s disease. We have investigated protein and lipid systems involved in the formation of these organelles and in the synthesis of the neuromelanin of human substantia nigra. Membrane and matrix proteins characteristic of lysosomes were found in neuromelanin-containing organelles at a lower number than in typical lysosomes, indicating a reduced enzymatic activity and likely impaired capacity for lysosomal and autophagosomal fusion. The presence of proteins involved in lipid transport may explain the accumulation of lipid bodies in the organelle and the lipid component in neuromelanin structure. The major lipids observed in lipid bodies of the organelle are dolichols with lower amounts of other lipids. Proteins of aggregation and degradation pathways were present, suggesting a role for accumulation by this organelle when the ubiquitin-proteasome system is inadequate. The presence of proteins associated with aging and storage diseases may reflect impaired autophagic degradation or impaired function of lysosomal enzymes. The identification of typical autophagy proteins and double membranes demonstrates the organelle’s autophagic nature and indicates that it has engulfed neuromelanin precursors from the cytosol. Based on these data, it appears that the neuromelanin-containing organelle has a very slow turnover during the life of a neuron and represents an intracellular compartment of final destination for numerous molecules not degraded by other systems. Nature Publishing Group UK 2018-06-05 /pmc/articles/PMC5988730/ /pubmed/29900402 http://dx.doi.org/10.1038/s41531-018-0050-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zucca, Fabio A.
Vanna, Renzo
Cupaioli, Francesca A.
Bellei, Chiara
De Palma, Antonella
Di Silvestre, Dario
Mauri, Pierluigi
Grassi, Sara
Prinetti, Alessandro
Casella, Luigi
Sulzer, David
Zecca, Luigi
Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease
title Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease
title_full Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease
title_fullStr Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease
title_full_unstemmed Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease
title_short Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease
title_sort neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988730/
https://www.ncbi.nlm.nih.gov/pubmed/29900402
http://dx.doi.org/10.1038/s41531-018-0050-8
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