19.12: The ADP/ATP Carrier Protein
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational states: cytoplasmic-open state and matrix-open state. As a result, the transporter's substrate-binding site is alternately accessible to each of the compartments for ADP/ATP binding.
Most eukaryotic cells express different isoforms of the ADP/ATP carrier protein. For instance, humans have four isoforms, AAC1, AAC2, AAC3, and AAC4, with varying expression patterns between cells. Irrespective of the isoforms, all ADP/ATP carrier proteins have notably higher substrate specificity than other transporters within the mitochondrial membranes. AAC recognizes each part of the nucleotide structure and allows only charged nucleotides to pass through. For instance, ATP has a charge of -4, and ADP carries a -3 charge, and both are, therefore, recognized by AAC protein. In contrast, AAC rejects any uncharged nucleotide, such as AMP, due to its charge selectivity.
Most transporters form large supercomplexes with other proteins. It was long believed that ADP/ATP carrier, phosphate carrier proteins, and the ATP synthase form a large complex called ATP synthasome. However, it is now known that ATP synthase forms dimers on the cristae tip. This arrangement renders only the rotating c-ring exposed to the lipid bilayer with no plausible binding sites for the transporters. Thus, the ACC functions independently in transporting ADP and ATP across the inner mitochondrial membrane.