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Adenine nucleotide translocator 1 (ANT1), also known as ADP/ATP translocase 1, is a nuclear-encoded protein located in the inner mitochondrial membrane that plays a fundamental role in cellular energy metabolism [1, 10]. It functions as an antiporter, exchanging mitochondrial ATP for cytosolic ADP, thereby ensuring a continuous supply of energy for cellular processes while maintaining the pool of substrates for oxidative phosphorylation [12]. Beyond its transport function, ANT1 is a critical component or regulator of the mitochondrial permeability transition pore (mPTP), making it a central player in the execution of apoptosis [3, 6]. Mutations in the SLC25A4 gene, which encodes ANT1, are associated with various mitochondrial disorders such as progressive external ophthalmoplegia and Senger's syndrome, often involving mitochondrial DNA deletions and muscle dysfunction [13, 15]. In the context of drug development, ANT1 is considered a potential target for cancer therapy due to its ability to trigger cell death when modulated by specific ligands or pro-apoptotic proteins like Bax [8, 11]. However, the high expression of ANT1 in the heart and skeletal muscle poses significant safety challenges, as unintended inhibition can lead to severe cardiomyopathy and metabolic failure [14, 16].
Inhibition of ADP/ATP exchange and modulation of the mitochondrial permeability transition pore (mPTP) to induce apoptosis [3, 6, 12].
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