Purified F-ATP synthase forms a Ca²⁺-dependent high-conductance channel matching the mitochondrial permeability transition pore.

ABSTRACT: The molecular identity of the mitochondrial megachannel (MMC)/permeability transition pore (PTP), a key effector of cell death, remains controversial. By combining highly purified, fully active bovine F-ATP synthase with preformed liposomes we show that Ca²⁺ dissipates the H⁺ gradient generated by ATP hydrolysis. After incorporation of the same preparation into planar lipid bilayers Ca²⁺ elicits currents matching those of the MMC/PTP. Currents were fully reversible, were stabilized by benzodiazepine 423, a ligand of the OSCP subunit of F-ATP synthase that activates the MMC/PTP, and were inhibited by Mg²⁺ and adenine nucleotides, which also inhibit the PTP. Channel activity was insensitive to inhibitors of the adenine nucleotide translocase (ANT)

SUBMITTER: Urbani A 

PROVIDER: S-EPMC6761146 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature