Induction of mitochondrial swelling in isolated pancreatic acini by excess lysine

The effects of excess lysine on in vitro morphological and functional changes of acinar cells and isolated mitochondria of rat pancreas were examined. In isolated acinar cells, excess lysine caused marked swelling of mitochondria as an early change, followed by dilatation of the endoplasmic reticulum and the appearance of autophagic vacuoles. Concomitantly, release of amylase from isolated acinar cells increased. Addition of excess lysine to suspensions of mitochondria also induced their swelling and inhibited their oxidative phosphorylation. The present study suggests that the first intracellular target of excess lysine in acinar cell damage is mitochondria and that lysine has the direct effect of depolarizing mitochondrial membranes, resulting in mitochondrial swelling and inhibition of oxidative phosphorylation.