It has been shown that interactions exist between sequential enzymes of the Krebs tricarboxylic acid cycle and that these enzymes also bind to proteins in the inner mitochondrial membrane. There still remain, however, several Krebs tricarboxylic acid cycle interactions that are not demonstrated and several which need to be better characterized. It is possible that these supramolecular complexes have not only a metabolic role but also a structural role in the mitochondria. An unresolved problem concerning mitochondrial structure is the molecular basis for the form of cristae, which show great variability within the same mitochondrion. This project will: 1) isolate and characterize the binding proteins for the inner membrane; and 2) investigate the molecular basis of cristae form. Cells are not simply "bags" of enzymes. Organization of the elements of cells, as well as cells themselves, allows efficient and economical use of the components of life. At the molecular level, an organized array of the enzymes of a metabolic sequence allows the attainment of higher fluxes with lower concentrations of each of the intermediates. A second benefit is that such organization does not tax the limited solvent capacity of cells. There seems to have been some evolutionary pressure for organization since some metabolic pathways exist as separate enzymes in organisms believed to represent early evolutionary conditions and exist as multifunctional enzymes in cells which are believed to have arisen later in evolution. This project will provide information in the role of multi-enzyme complexes in the formation of cell membranes.***//
