The adenine nucleotide translocase family underlies cardiac ischemia-reperfusion injury through the mitochondrial permeability pore independently of cyclophilin D.

ABSTRACT: The mitochondrial permeability transition pore (mPTP) is implicated in cardiac ischemia-reperfusion (I/R) injury. During I/R, elevated mitochondrial Ca²⁺ triggers mPTP opening, leading to necrotic cell death. Although nonessential regulators of this pore are characterized, the molecular identity of the pore-forming component remains elusive. Two of these genetically verified regulators are cyclophilin D (CypD) and the adenine nucleotide translocase (ANT) family. We investigated the ANT/CypD relationship in mPTP dynamics and I/R injury. Despite lacking all ANT isoforms, Ca²⁺-dependent mPTP opening persisted in cardiac mitochondria but was desensitized. This desensitization conferred resistance to I/R injury in ANT-deficient mice. CypD is hypothesized to trigger mPTP op

SUBMITTER: Patel P 

PROVIDER: S-EPMC11633734 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature