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Sideroflexin 3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology.

TitleSideroflexin 3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology.
Publication TypeJournal Article
Year of Publication2017
AuthorsAmorim IS, Graham LC, Carter RN, Morton NM, Hammachi F, Kunath T, Pennetta G, Carpanini SM, Manson JC, Lamont DJ, Wishart TM, Gillingwater TH
JournalJ Cell Sci
Volume130
Issue2
Pagination325-331
Date Published2017 Jan 15
ISSN1477-9137
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.

DOI10.1242/jcs.194241
Alternate JournalJ. Cell. Sci.
PubMed ID28049716
PubMed Central IDPMC5278670
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