Research ArticleParkinson’s Disease

α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson’s disease

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Science Translational Medicine  08 Jun 2016:
Vol. 8, Issue 342, pp. 342ra78
DOI: 10.1126/scitranslmed.aaf3634

α-Synuclein disrupts the mitochondrial protein import business

α-Synuclein accumulation and mitochondrial dysfunction are central to the pathogenesis of most forms of Parkinson’s disease and appear to intersect, but how the two are related to each other has remained elusive. Now, Di Maio and colleagues report that specific forms of wild-type α-synuclein, such as oligomeric and dopamine-modified forms, but not the monomeric or fibrillar forms, bind with high affinity to the mitochondrial receptor TOM20. This results in impaired import of proteins required for mitochondrial function and leads to senescence of mitochondria, which show reduced respiration and increased production of reactive oxygen species. This study also highlights potential ways to prevent this deleterious interaction and its downstream consequences.