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

Α-Synuclein accumulation and mitochondrial dysfunction have both been strongly implicated in the pathogenesis of Parkinson's disease (PD), and the two appear to be related. Mitochondrial dysfunction leads to accumulation and oligomerization of α-synuclein, and increased levels of α-synuclein cause mitochondrial impairment, but the basis for this bidirectional interaction remains obscure. We now report that certain posttranslationally modified species of α-synuclein bind with high affinity to the TOM20 (translocase of the outer membrane 20) presequence receptor of the mitochondrial protein import machinery. This binding prevented the interaction of TOM20 with its co-receptor, TOM22, and impaired mitochondrial…

• UD
  U.S. Department of Veterans Affairs

  Award: 1I01BX000548
• DC
  DSF Charitable Foundation
• AP
  American Parkinson Disease Association
• FR
  Fondazione Ri.Med
• NI
  National Institutes of Health

  Awards: P50AG005133, ES022644, ES020718, NS065789, ES020327, NS095387, AG026389, NS059806