The presence of two classes of high-affinity cyclosporin A binding sites in mitochondria. Evidence that the minor component is involved in the opening of an inner-membrane Ca(2+)-dependent pore.
Eur J Biochem
The inner membrane of rat liver mitochondria contains a reversible Ca(2+)-dependent pore, opening of which is largely blocked by cyclosporin A. Analyses of [3H]cyclosporin binding to rat liver mitochondria demonstrate two classes of high-affinity binding site with capacities of less than 5 pmol and approximately 60 pmol cyclosporin.mg mitochondrial protein-1 in addition to partitioning into membrane phospholipids (0.03 pmol.mg mitochondrial protein.nM-1). Direct measurement [14C]sucrose entry into the matrix space indicates that cyclosporin A inhibits pore opening by interacting with the low-capacity sites. The same low-capacity sites (Kd cyclosporin, 8 nM) are possibly attributable to peptidylprolyl cis-trans-isomerase, although investigation of pore state interconversion from the rapid kinetics of [14C]sucrose entrapment in the matrix space does not indicate that cyclosporin-sensitive prolyl isomerization occurs at the actual step of pore opening/closure. It is suggested that the low-capacity cyclosporin-binding component may stabilize the open pore state; this is supported by the observations that Ca2+ decreases cyclosporin binding to this component and that cyclosporin brings about closure of the pre-opened pore. The implications for the possible number of functional pores in mitochondria are discussed.
|Title:||The presence of two classes of high-affinity cyclosporin A binding sites in mitochondria. Evidence that the minor component is involved in the opening of an inner-membrane Ca(2+)-dependent pore.|
|Keywords:||Amino Acid Isomerases, Animals, Binding Sites, Calcium Channels, Carrier Proteins, Cyclosporins, Egtazic Acid, Fatty Acids, Nonesterified, Male, Mitochondria, Liver, Peptidylprolyl Isomerase, Rats, Rats, Inbred Strains, Submitochondrial Particles|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
Archive Staff Only