TY - JOUR T1 - Optical Reporters for the Conformation of α-Synuclein Reveal a Specific Interaction with Mitochondria JF - The Journal of Neuroscience JO - J. Neurosci. SP - 12305 LP - 12317 DO - 10.1523/JNEUROSCI.3088-08.2008 VL - 28 IS - 47 AU - Ken Nakamura AU - Venu M. Nemani AU - Erika K. Wallender AU - Katrin Kaehlcke AU - Melanie Ott AU - Robert H. Edwards Y1 - 2008/11/19 UR - http://www.jneurosci.org/content/28/47/12305.abstract N2 - The aggregation of abnormally folded proteins is a defining feature of neurodegenerative disease, but it has not previously been possible to assess the conformation of these proteins in a physiologically relevant context, before they form morphologically recognizable aggregates. We now describe FRET-based reporters for the conformation of α-synuclein, a protein central to the pathogenesis of Parkinson's disease (PD). Characterization in vitro shows that α-synuclein adopts a relatively “closed” conformation in solution that converts to “open” on membrane binding. In living cells, the closed conformation predominates. In neurons, however, cell bodies contain a much larger proportion of the open conformation than synaptic boutons. To account for these differences, we also used the reporters to characterize the interaction with native membranes. We find that the conformation of α-synuclein responds selectively to mitochondria, indicating a direct link between α-synuclein and an organelle strongly implicated in the pathogenesis of PD. ER -