Mitochondrial conformation and swelling-contraction reactivity during early liver regeneration

Abstract

Studies of mitochondrial respiratory control and swelling contraction activity during early cell regeneration after partial hepatectomy have revealed a selective defect in the rate of substrate-supported, phosphate-induced mitochondrial swelling. Swelling profiles induced by Fe(2-) or Cu(2-) revealed no differences between sham-operated and partially hepatectomized mice, which suggests no defects in -SH group composition or ability to form lipid peroxides. The specific activity of mitochondrial cytochrome c oxidase was unchanged. There was no significant mitochondrial swelling in situ as determined from mitocrit and mitochondrial protein ratios. A significant decline in respiratory control and efficiency of oxidative phosphorylation was found in mitochondria from animals 8 and 24 hours after partial hepatectomy, partially reversed by bovine serum albumin. No significant change in ADP:O ratio was noted and the decrease in RCI was due primarily to a significant decline in state 3 respiration rate. In situ electron microscopic studies of mitochondria failed to reveal significant abnormalities during early cell regeneration apart from decrease in numbers of matrix granules, focal matrix rarefaction and predominance of round forms. Electron microscopic studies of mitochondria after in vitro phosphate-induced swelling experiments showed no differences between sham and partially hepatectomized animals, but revealed two distinct populations of mitochondria, the predominant form (type III) showing distortion, matrix lucency and outer membrane rupture. ATP induced a diminished reversal in light scattering in partially hepatectomized mitochondria even when examined at 20 minutes, manifested as an increase in numbers of orthodox mitochondrial forms at the expense of the swollen type III forms. The pathogenesis of the impaired respiratory control and phosphate-induced swelling is unknown, but analogous observations have been found in mitochondria harvested from cells in which abnormal accumulations of free fatty acids have been demonstrated.