Adenine nucleotide translocase is a mitochondrial enzyme which plays a primary role in the cellular respiration process. The correct functioning of mitochondria is strictly dependent on this enzymatic system, which is located on the membrane and which is physiologically implicated in the transfer of neo-synthesized ATP molecules from the inner side towards the cytoplasm. In exchange, adenine nucleotide translocase moves an ADP molecule from the cytosol to the inner side of the mitochondrium, therefore representing proper exchanging system.
Adenine nucleotide translocase is characterized by a relatively low affinity for its substrate, but the exchanging process is overall well balanced since these enzymes are massively expressed on mitochondrial membrane – they represent more than the 10% of the total mitochondrial proteins. Moreover, the ATP/ADP exchanging process gives rise to a charge differential between inner and outer sides of the mithochondrium. As of today, many isoforms of this enzyme are known and are mainly related to the diverse subtypes of tissues. For example, muscle/cardiac fibers are characterized by high expression levels of the Ant-1 isoform, whereas Ant-4 is more typical of testis. Other isoforms, although they still exhibit a certain grade of tropism, are more ubiquitous .
Adenine nucleotide translocase hence is strictly coupled with oxydative phosphorylation and with the cellular respiration process itself, since it represents the last essential step of the entire process. The production of ATP is probably one of the most elegant examples of perfect exploitation of substrates to obtain energy under the form of chemical energy; nonetheless, ATP requires to be moved from the production site to the utilization sites, and to this aim the first step is given by its translocation from the inner side of the mitochondria to the cytosol. Only after this passage the energy produced in form of ATP will become available for cells. Moreover, the respiration process can also be seen as a extraordinary example of re-utilization of “waste” products, such as ADP. Although defining ADP as a waste product may be rather simplified and reductive, the re-introduction of this molecule operated by adenine-nucleotide translocase inside the mitochondria allows the subsequent addition of a phosphate molecule and thus the production of a novel ATP one. This last process is, again, possible only thanks to the presence of adenine nucleotide translocase. In practice, a malfunctioning of adenine nucleotide translocase gives rise to deleterious effects and to a decoupling of the oxydative phosphorylation process, resulting eventually in the blockade of the whole respiration process .
Moreover, altered expression levels of this enzyme give rise to a drastically decreased outcome of ATP molecules and to an overproduction of reactive-oxygen species (ROS), which are directly implicated in tissue damage and in the development of pre-cancerous lesions which may eventually lead to an augmented risk of insurgence of neoplasms. Nonetheless, the human inherited deficiency of Ant1 is thought to be at the bases of Senger’ s syndrome, a disease typically accompanied by mithocondrial myopathy, cataracts, lactic acidosis and cardiac hypertrophy. Deleterious conditions may also be the result of an over-expression of adenine nucleotide translocase: facioscapulohumeral muscolar dystrophy (FSHD), an inherited neuromuscolar disease characterized by muscle weakness, is thought to be caused by an aberrantly high expression of this enzyme. Moreover, the overexpression of ANT2 isoform has been shown to be typical of hormonoresponsive cancers, such as breast cancer, probably due to an adaptive mechanism in response to hypoxic conditions .
Overall, then, adenine nucleotide translocase represents an essential brick in the context of cellular respiration. Since respiration is probably the most important biochemical phenomenon for the production of energy after the introduction of nutrients, adenine nucleotide translocase is further characterized by an intrinsic biological importance.