Giant mitochondria induced in rat pancreatic exocrine cells by ethanol and iron.

Abstract

Mitochondria are sensitive indicators of cellular pathology. Under certain circumstances, these organelles respond to cellular insult by a marked increase in size, resulting in the formation of giant mitochondria (megamitochondria). Ethanol has been implicated in the induction of giant mitochondria in rat hepatocytes. Since ethanol is reported 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. Diets were administered via a chronically implanted gastrostomy catheter. Rats were segregated in four groups: 1) basic high-fat diet, 2) ethanol and a high 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 extirpated and processed for and examined by transmission electron microscopy. Mitochondria in rats on the basic high fat diet resemble those in untreated controls. With ethanol and a high-fat diet, some mitochondria in virtually every exocrine cell are profoundly altered. Such organelles, which are of normal size, have undergone rearrangement of their internal membranes, with three of four parallel cristae residing at one or both poles of spherical to ovate mitochondria. In rats receiving both ethanol and carbonyl iron, giant mitochondria are present in pancreatic exocrine cells. Except for their size, megamitochondria in many cases are virtual likenesses of the altered mitochondria in the alcohol-high-fat rats, having several stacked cristae at either pole and an enhanced matrix compartment. Many of the giant mitochondria have at least one expanded crista, which contains packets of helically coiled filaments. When control rats are fed carbonyl iron without ethanol, the pancreatic mitochondria display a marked propensity for forming clusters of tightly interlocked organelles, formations that may be a prelude to mitochondrial fusion. It appears that iron supplementation sets the stage for organelle fusion, hence enlargement, with the ethanol providing the stimulus for fusion to actually take place, and controlling the final morphology of the resultant megamitochondria.