A mitochondrial megachannel resides in monomeric F<sub>1</sub>F<sub>O</sub> ATP synthase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31862883.
- Also identified by DOI 10.1038/s41467-019-13766-2 and PMC identifier 6925261.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Purified mitochondrial ATP synthase has been shown to form Ca<sup>2+</sup>-activated, large conductance channel activity similar to that of mitochondrial megachannel (MMC) or mitochondrial permeability transition pore (mPTP) but the oligomeric state required for channel formation is being debated. We reconstitute purified monomeric ATP synthase from porcine heart mitochondria into small unilamellar vesicles (SUVs) with the lipid composition of mitochondrial inner membrane and analyze its oligomeric state by electron cryomicroscopy. The cryo-EM density map reveals the presence of a single ATP synthase monomer with no density seen for a second molecule tilted at an 86<sup>o</sup> angle relative to the first. We show that this preparation of SUV-reconstituted ATP synthase monomers, when fused into giant unilamellar vesicles (GUVs), forms voltage-gated and Ca<sup>2+</sup>-activated channels with the key features of mPTP. Based on our findings we conclude that the ATP synthase monomer is sufficient, and dimer formation is not required, for mPTP activity.
Medical subject headings
- Mitochondrial Proton-Translocating ATPases
- Protein Subunits