Adenine nucleotide translocator

Adenine nucleotide translocator (ANT), also known as the ADP/ATP translocase or mitochondrial ADP/ATP carrier, exchanges free ATP with free ADP across the inner mitochondrial membrane. ANT is the most abundant protein in the inner mitochondrial membrane and belongs to mitochondrial carrier family. Adenine nucleotide translocator (ANT), also known as the ADP/ATP translocase or mitochondrial ADP/ATP carrier, exchanges free ATP with free ADP across the inner mitochondrial membrane. ANT is the most abundant protein in the inner mitochondrial membrane and belongs to mitochondrial carrier family. ANT has long been thought to function as a homodimer, but this concept was challenged by the projection structure of the yeast Aac3p solved by electron crystallography, which showed that the protein was three-fold symmetric and monomeric, with the translocation pathway for the substrate through the centre. The atomic structure of the bovine ANT confirmed this notion, and provided the first structural fold of a mitochondrial carrier. Further work has demonstrated that ANT is a monomer in detergents and functions as a monomer in mitochondrial membranes. ANT transports the free, i.e. deprotonated, non-Magnesium, non-Calcium bound forms of ADP and ATP, in a 1:1 ratio. Transport is fully reversible, and its directionality is governed by the concentrations of its substrates (ADP and ATP inside and outside mitochondria), the chelators of the adenine nucleotides, and the mitochondrial membrane potential. The relationship of these parameters can be expressed by an equation solving for the 'reversal potential of the ANT' (Erev_ANT), a value of the mitochondrial membrane potential at which no net transport of adenine nucleotides takes place by the ANT. The ANT and the F0-F1 ATP synthase are not necessarily in directional synchrony. Apart from exchange of ADP and ATP across the inner mitochondrial membrane, the ANT also exhibits an intrinsic uncoupling activity ANT is an important modulatory but not structural component of the mitochondrial permeability transition pore which can open and lead to cell death through apoptosis or necrosis. The translocator cycles between two states, called the cytoplasmic and matrix state, opening up to these compartments in an alternating way. There are structures available that show the translocator locked in a cytoplasmic state by the inhibitor carboxyatractyloside, or in the matrix state by the inhibitor bongkrekic acid. In humans, there exist three paraologous ANT isoforms: