The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore.

ABSTRACT: The mitochondrial permeability transition pore (mPTP) is a channel in the inner mitochondrial membrane whose sustained opening in response to elevated mitochondrial matrix Ca²⁺ concentrations triggers necrotic cell death. The molecular identity of mPTP is unknown. One proposed candidate is the mitochondrial ATP synthase, whose canonical function is to generate most ATP in multicellular organisms. Here, we present mitochondrial, cellular, and in vivo evidence that, rather than serving as mPTP, the mitochondrial ATP synthase inhibits this pore. Our studies confirm previous work showing persistence of mPTP in HAP1 cell lines lacking an assembled mitochondrial ATP synthase. Unexpectedly, however, we observe that Ca²⁺-induced pore opening is markedly sensitized by loss of

SUBMITTER: Pekson R 

PROVIDER: S-EPMC10743364 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature