Exploring the multifaceted role of adenosine nucleotide translocase 2 in cellular and disease processes: A comprehensive review

Adenosine nucleotide translocases (ANTs) are a family of proteins abundant in the inner mitochondrial membrane, primarily responsible for shuttling ADP and ATP across the mitochondrial membrane. Additionally, ANTs are key players in balancing mitochondrial energy metabolism and regulating cell death. ANT2 isoform, highly expressed in undifferentiated and proliferating cells, is implicated in the development and drug resistance of various tumors. We conduct a detailed analysis of the potential mechanisms by which ANT2 may influence tumorigenesis and drug resistance. Notably, the significance of ANT2 extends beyond oncology, with roles in non-tumor cell processes including blood cell development, gastrointestinal motility, airway hydration, nonalcoholic fatty liver disease, obesity, chronic kidney disease, and myocardial development, making it a promising therapeutic target for multiple pathologies. To better understand the molecular mechanisms of ANT2, this review summarizes the structural properties, expression patterns, and basic functions of the ANT2 protein. In particular, we review and analyze the controversy surrounding ANT2, focusing on its role in transporting ADP/ATP across the inner mitochondrial membrane, its involvement in the composition of the mitochondrial permeability transition pore, and its participation in apoptosis.