Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F₁ subcomplex.

ABSTRACT: Mitochondrial ATP synthase is vital not only for cellular energy production but also for energy dissipation and cell death. ATP synthase c-ring was suggested to house the leak channel of mitochondrial permeability transition (mPT), which activates during excitotoxic ischemic insult. In this present study, we purified human c-ring from both eukaryotic and prokaryotic hosts to biophysically characterize its channel activity. We show that purified c-ring forms a large multi-conductance, voltage-gated ion channel that is inhibited by the addition of ATP synthase F₁ subcomplex. In contrast, dissociation of F₁ from F_O occurs during excitotoxic neuronal death suggesting that the F₁ constitutes the gate of the channel. mPT is known to dissipate the osmot

SUBMITTER: Mnatsakanyan N 

PROVIDER: S-EPMC9433415 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature