bioimagesUnknownhiPSC derived neuronshttps://www.ebi.ac.uk/biostudies/studies/S-BIAD465bioimagesProtocolsStudy ComponentorganisationStudy ProtocolsNoemi Esteras Sonia GhandiBhanu P. SinghMathew H. HorrocksGurvier S. ViridiZeniba ShadmanJames R. Evans David J. Clarke Laura TosattoMinee L. Choi Lucy Collinson Andrey Y. AbramovCatherine MaclachlanKatie Morris Anna WernickMaragarida RodriguesPlamena R. AngelovaAlexey V. BerezhnovEvgenia FedotovaKiani JeacockAlexandre ChappardDilan Athauda David KlenermanChris PeddieDaniel Little Tilo KunathSuman DePaul Gissen Andrey Y. VinikurovWeilia ZhangfalseStructural conversion of α-synuclein at the mitochondria induces neuronal toxicity Aggregation of alpha-synuclein (α-Syn) drives Parkinson’s disease, although the initial stages of self-assembly and structural conversion have not been captured inside neurons. We track the intracellular conformational states of α-Syn utilizing a single-molecule Förster resonance energy transfer (smFRET) biosensor and show that α-Syn converts from its monomeric state to form two distinct oligomeric states in neurons in a concentration-dependent and sequence-specific manner. 3D FRET-Correlative light and electron microscopy (FRET- CLEM) reveals the structural organization and location of aggregation hotspots inside the neuron. Notably, multiple intracellular seeding events occur preferentially on membrane surfaces, especially at the mitochondrial membranes. The mitochondrial lipid, cardioli2022-05-11T00:00:00Z2022-05-27T11:11:06.681Z2022-05-27T11:11:06.681ZS-BIAD465