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Defining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase.

ABSTRACT: F-ATP synthase is a leading candidate as the mitochondrial permeability transition pore (PTP) but the mechanism(s) leading to channel formation remain undefined. Here, to shed light on the structural requirements for PTP formation, we test cells ablated for g, OSCP and b subunits, and ρ⁰ cells lacking subunits a and A6L. Δg cells (that also lack subunit e) do not show PTP channel opening in intact cells or patch-clamped mitoplasts unless atractylate is added. Δb and ΔOSCP cells display currents insensitive to cyclosporin A but inhibited by bongkrekate, suggesting that the adenine nucleotide translocator (ANT) can contribute to channel formation in the absence of an assembled F-ATP synthase. Mitoplasts from ρ⁰ mitochondria display PTP currents indistinguishable from their wild-type counterparts. In this work, we show that peripheral stalk subunits are essential to turn the F-ATP synthase into the PTP and that the ANT provides mitochondria with a distinct permeability pathway.

SUBMITTER: Carrer A

PROVIDER: S-EPMC8355262 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Dimers of mitochondrial ATP synthase form the permeability transition pore.

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Ca2+ binding to F-ATP synthase ? subunit triggers the mitochondrial permeability transition.

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Genetic manipulation of the cardiac mitochondrial phosphate carrier does not affect permeability transition.

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Persistence of the mitochondrial permeability transition in the absence of subunit c of human ATP synthase.

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An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore.

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| S-EPMC4115574 | biostudies-literature

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