P4‐514: TRACKING ENLARGED PERIVASCULAR SPACES FROM CLINICAL MRI TO POST‐MORTEM MRI GUIDED HISTOPATHOLOGY

still being debated. Now, we purified and reconstituted monomeric ATP synthase from porcine heart mitochondria into small unilamellar lipid vesicles (SUVs) and analyzed its oligomeric state by single-particle electron cryomicroscopy. Results: Here, we present the cryo-EM structure of functionally active monomeric ATP synthase in SUVs at w16 A resolution. The patch-clamp recordings reveal that this preparation of SUV-reconstituted ATP synthase monomers, when fused into giant unilamellar vesicles (GUVs), form voltage-gated and Ca-activated channels with the key features of mPTP. Conclusions: Based on our findings we conclude that the ATP synthase monomer is sufficient, and dimer formation is not required for its megachannel activity. In-depth structural analysis of ATP synthase will reveal its “open channel” conformation and will lead to a structure-based drug design of specific therapeutic compounds for the treatment of Alzheimer’s disease and other neurological disorders.