GIANT MITOCHONDRIA INDUCED IN RAT PANCREATIC EXOCRINE CELLS BY ETHANOL AND IRON

Background: Mitochondria are sensitive indicators of cellular patholog y. Under certain circumstances, these organelles respond to cellular i nsult by a marked increase in size, resulting in the formation of gian t mitochondria (megamitochondria). Ethanol has been implicated in the induction of giant mitochondria in rat hepatocytes. Since ethanol is r eported to affect pancreatic mitochondria, we examined this organ for evidence of mitochondrial giantism in rats administered ethanol and a relatively small amount of supplementary iron. Methods: Diets were adm inistered via a chronically implanted gastrostomy catheter. Rats were segregated in four groups: 1) basic high-fat diet, 2) ethanol and a hi gh fat diet, 3) carbonyl iron and a high-fat diet, and 4) ethanol and carbonyl iron combined with a high-fat diet. After the animals were on their respective diets for 16 weeks, specimens of pancreas were extir pated and processed for and examined by transmission electron microsco py. Results: Mitochondria in rats on the basic high fat diet resemble those in untreated controls. With ethanol and a high-fat diet, some mi tochondria in virtually every exocrine cell are profoundly altered. Su ch organelles, which are of normal size, have undergone rearrangement of their internal membranes, with three or four parallel cristae resid ing at one or both poles of spherical to ovate mitochondria. In rats r eceiving both ethanol and carbonyl iron, giant mitochondria are presen t in pancreatic exocrine cells. Except for their size, these megamitoc hondria in many cases are virtual likenesses of the altered mitochondr ia in the alcohol-high-fat rats, having several stacked cristae at eit her pole and an enhanced matrix compartment. Many of the giant mitocho ndria have at least one expanded crista, which contains packets of hel ically coiled filaments. When control rats are fed carbonyl iron witho ut ethanol, the pancreatic mitochondria display a marked propensity fo r forming clusters of tightly interlocked organelles, formations that may be a prelude to mitochondrial fusion. Conclusions: It appears that iron supplementation sets the stage for organelle fusion, hence enlar gement, with the ethanol providing the stimulus for fusion to actually take place, and controlling the final morphology of the resultant meg amitochondria. (C) 1996 Wiley-Liss, Inc.