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Sideroflexin 3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology
- Source :
- Journal of Cell Science
- Publication Year :
- 2016
-
Abstract
- α-Synuclein plays a central role in Parkinson's disease, where it contributes to the vulnerability of synapses to degeneration. However, the downstream mechanisms through which α-synuclein controls synaptic stability and degeneration are not fully understood. Here, comparative proteomics on synapses isolated from α-synuclein−/− mouse brain identified mitochondrial proteins as primary targets of α-synuclein, revealing 37 mitochondrial proteins not previously linked to α-synuclein or neurodegeneration pathways. Of these, sideroflexin 3 (SFXN3) was found to be a mitochondrial protein localized to the inner mitochondrial membrane. Loss of SFXN3 did not disturb mitochondrial electron transport chain function in mouse synapses, suggesting that its function in mitochondria is likely to be independent of canonical bioenergetic pathways. In contrast, experimental manipulation of SFXN3 levels disrupted synaptic morphology at the Drosophila neuromuscular junction. These results provide novel insights into α-synuclein-dependent pathways, highlighting an important influence on mitochondrial proteins at the synapse, including SFXN3. We also identify SFXN3 as a new mitochondrial protein capable of regulating synaptic morphology in vivo.<br />Summary: Comparative proteomics revealed that mitochondrial proteins are a major target for α-synuclein. Sideroflexin 3 (SFXN3) was identified as one α-synuclein-dependent mitochondrial protein capable of altering synaptic morphology in vivo.
- Subjects :
- Mice, Knockout
Neuromuscular Junction
Short Report
Membrane Proteins
Synapse
nervous system diseases
Mitochondria
Mice, Inbred C57BL
Mitochondrial Proteins
Alpha-synuclein
Drosophila melanogaster
Gene Ontology
Mitochondrial Membranes
Synapses
Animals
Drosophila Proteins
Humans
Sideroflexin 3
Neurodegeneration
Energy Metabolism
Cation Transport Proteins
Subjects
Details
- ISSN :
- 14779137
- Volume :
- 130
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of cell science
- Accession number :
- edsair.pmid..........bd5cd3ca723a90c81b06b084e5d18c6e