MITOCHONDRIAL ALTERATIONS INDUCED BY ASPIRIN IN RAT HEPATOCYTES EXPRESSING MITOCHONDRIALLY TARGETED GREEN FLUORESCENT PROTEIN (MTGFP)

Mitochondria in primary living hepatocytes were visualized in cells tr ansfected with a chimeric plasmid encoding for the green fluorescent p rotein (GFP) of Aequorea victor ia engineered to be specifically targe ted to mitochondria, as described recently (Rizzuto et al. (1995) Curr . Biol. 5, 635-642). The identification of the fluorescent organelles as authentic mitochondria was confirmed by double labeling with rhodam ine 123. Acetylsalicylate treatment of hepatocytes induced in mitochon dria typical morphological alterations closely analogous to the swelli ng promoted by acetylsalicylate in isolated mitochondria. Cyclosporin A, which in isolated mitochondria prevents the changes induced by acet ylsalicylate, had no protective action but induced per se specific alt erations in the morphology of mitochondria. Moreover, exposure of hepa tocytes to cyclosporin A followed by acetylsalicylate caused the same mitochondrial changes induced by each of the two compounds separately. The structural alterations caused by acetylsalicylate were constantly associated with a decrease in mitochondrial urea synthesis and cell v iability.