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P4‐513: ACTIVATION OF FERROPTOSIS, AN IRON‐DEPENDENT FORM OF NON‐APOPTOTIC DEATH IN NEURONS
Author(s) -
Plascencia-Villa German,
Perry George
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.08.059
Subject(s) - programmed cell death , neurodegeneration , microbiology and biotechnology , oxidative stress , necroptosis , mitochondrion , biology , apoptosis , reactive oxygen species , transcriptome , neuroinflammation , chemistry , biochemistry , immunology , gene expression , disease , pathology , medicine , inflammation , gene
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.