The proton pump spares activity of the sodium and hydrogen exchanger and secondary accumulation of calcium through the sodium and calcium exchanger. Previously, we showed that ischemia-reperfusion injury resulted in apoptosis of cardiomyocytes. We are now cloning the cardiac caspases. Acidification may be necessary for activation of the endonuclease responsible for degradation of DNA during apoptosis. In a cell culture model of cystic fibrosis, the elevated resting pH of the cells interferes with cytoplasmic acidification and apoptosis.
Mitochondrial function is greatly impaired during apoptosis.
This defunctionalization is characterized by dissociation of the cytochrome from the electron transport chain and is due to the action of a cytosolic factor known as cytochrome c inactivating factor of apoptosis. Bcl-2 opposes the action of this factor. Purification of the factor is under way, in collaboration with B. Babior, Department of Molecular and Experimental Medicine. Mitochondrial inactivation is a feature of the response of neuronlike PC12 cells exposed to the amyloidogenic peptide derived from amyloid precursor protein, which is elevated in patients with Alzheimer's disease. Mitochondrial abnormalities are a general feature of neurodegenerative diseases, and cytochrome oxidase defects are implicated in Alzheimer's disease.