Elucidating the transport mechanism of the mitochondrial ADP/ATP carrier
The aim was to find computational solutions with which to identify the fundamental transport mechanism of mitochondrial carriers. The mitochondrion is a special compartment of the human cell where components of sugar and fat are broken down to generate energy in the form of ATP. ATP is the chemical fuel used by the rest of the cell to carry out its activities. The mitochondrion is enclosed by a membrane that is impermeable to small organic molecules. Transport across the membrane is carried out by mitochondrial carriers that bind compounds on one side of the membrane and then carry it through the membrane for release on the other side.
We used quantum mechanical calculations to determine the interaction energy involved in substrate binding to relate it to the interaction energy of salt bridge networks. These networks regulate the access of substrates to the central binding site and are critical for efficient transport. We discovered that the two networks have equivalent interaction energies, which will optimise the transport rate of substrates across the mitochondrial membrane. At the time of writing experimental methods are being developed to verify these values.
We determined the motions of the three domains that constitute the mitochondrial carrier. Since none of the available computational methods could be applied, a new iterative computational approach was developed and tried that revealed the basic structural transport mechanism. This finding constitutes a fundamental contribution to the field. In the meantime the mechanism has been verified by experimental work and is the subject of an article intended for publication by a high impact journal.
PDF The transport mechanism of the mitochondrial ADP/ATP carrier.E.R.S. Kunji, A. Aleksandrova, M.S. King, H. Majd, V.L. Ashton, E. Cerson, R. Springett, M. Kibalchenko, S. Tavoulari, P.G. Crichton, J.J. Ruprecht
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (2016) doi:10.1016/j.bbamcr.2016.03.015