Amorim, IS;
Graham, LC;
Carter, RN;
Morton, NM;
Hammachi, F;
Kunath, T;
Pennetta, G;
... Gillingwater, TH; + view all
(2017)
Sideroflexin 3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology.
J Cell Sci
, 130
(2)
pp. 325-331.
10.1242/jcs.194241.
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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.
| Type: | Article |
|---|---|
| Title: | Sideroflexin 3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology. |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/jcs.194241 |
| Publisher version: | https://doi.org/10.1242/jcs.194241 |
| Language: | English |
| Additional information: | © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | Alpha-synuclein, Mitochondria, Neurodegeneration, Sideroflexin 3, Synapse, Animals, Cation Transport Proteins, Drosophila Proteins, Drosophila melanogaster, Energy Metabolism, Gene Ontology, Humans, Membrane Proteins, Mice, Inbred C57BL, Mice, Knockout, Mitochondrial Membranes, Mitochondrial Proteins, Neuromuscular Junction, Synapses, alpha-Synuclein |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10053270 |
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