ABSTRACT

The "chemiosmotic hypothesis" was originally developed by P. Mitchell in 1961 to account for the coupling of mitochondrial electron transport to the synthesis of Adenosine triphosphate (ATP). The discovery of a proton-translocating MgATPase in the secretory granule of adrenal medullary chromaffin cells was made as a result of investigations into the mechanism of catecholamine transport across the granule membrane. In the case of secretory granules the direction of the electrochemical proton gradient is opposite to that found with mitochondria because the proton-translocating ATPase present in the granule membrane pumps protons into the intragranular space. In the process of exocytosis, after secretory granules have fused with the plasma membrane of the cell, the barrier separating the granule interior from the extracellular medium undergoes breakage, or fission. The resulting transport of anions down their concentration gradient into the granule coupled to the proton-translocating MgATPase in the granule membrane might then provoke fission of the fused membrane complex by osmotic lysis.