Adenine Nucleotide Translocase at the Virus–Mitochondria Interface: A Conceptual Framework for Viral Mitochondrial Modulation

Mitochondria are control points in viral infection, integrating energy metabolism, cell-death decisions and innate immune signaling. Adenine nucleotide translocase (ANT), the mitochondrial ADP/ATP carrier, is strategically positioned by coupling oxidative phosphorylation to cellular energy demand while also influencing membrane permeability, mitochondrial quality control and stress signaling. This review examines ANT at the virus–mitochondria interface across distinct levels of mechanistic evidence, ranging from direct viral targeting of ANT isoforms to indirect convergence on ANT-linked mitochondrial pathways, and applies this conceptual framework to enterovirus-associated cardiac disease and post-infectious ANT autoimmunity. Viral proteins and miRNAs can engage or regulate distinct ANT isoforms to promote apoptosis, stabilize infected cells, support therapy resistance or reshape mitochondrial metabolism. Beyond these direct mechanisms, viral remodeling of oxidative phosphorylation, mitochondrial membrane potential, redox balance, mitophagy and mitochondrial nucleic-acid release alters the functional state in which ANT operates, even when ANT dependence has not been demonstrated. In the heart, enterovirus- and Coxsackievirus-associated myocarditis shows how ANT isoform remodeling, impaired ADP/ATP exchange, anti-ANT immunity and cytokine-driven immune amplification converge on chronic cardiac injury. ANT therefore emerges as an isoform- and context-sensitive mitochondrial interface at which viral infection, bioenergetic dysfunction, innate immune activation and post-infectious disease processes may converge.