F1F0 type ATPases are found in mitochondria of animal and plant cells, in chloroplasts of plant cells, and in the plasma membrane of bacteria. They are responsible for more than 95% of the ATP production in cells and also function as an ATPase, using the energy derived from cleavage of ATP to generate a proton gradient, which is then used for substrate and ion transport. Defects in the mitochondrial F1F0 type ATPase can be the primary cause, and are often a secondary consequence, of several human diseases. The structure of this complicated enzyme, and its mechanisms of functioning -- particularly the way in which the conversion of chemical energy and chemiosmotic energy are interconverted -- are poorly understood. We are studying the structure of the F1F0 from Escherichia coli (ECF1F0) by a number of different approaches including cryoelectron microscopy, chemical cross linking, and nuclear magnetic resonance studies. Our immediate goal is to characterize the delta and b subunits structurally, and understand their arrangement in the intact F1F0 complex. We believe that these subunits form a scaffold (a stator) that fixes the alpha3beta3 domain to the F0 part of the complex, thereby allowing the rotation of a mobile element made up of the gamma and epsilon subunits. Our idea is that this mobile element links the three different catalytic sites, in turn, with a single proton channel in the F0 to maximize the efficiency of energy coupling.