Changes in physicochemical properties of mitochondrial membranes during the formation process of megamitochondria induced by hydrazine |
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| Authors: | T Wakabayashi K Yamashita K Adachi K Kawai M Iijima K Gekko T Tsudzuki J Popinigis M Momota |
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| Affiliation: | 1. Division of Human Genetics, Children''s Hospital of Philadelphia, Philadelphia, PA, USA;2. Division of Pathology and Laboratory Medicine, Children''s Hospital of Philadelphia, Philadelphia, PA, USA;4. Division of Neuroradiology, Children''s Hospital of Philadelphia, Philadelphia, PA, USA;5. University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA;2. Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain;3. Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain;4. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain |
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| Abstract: | Changes in some biochemical and physico-chemical properties of rat liver mitochondrial membranes during the formation process of megamitochondria induced by hydrazine were analyzed. Hepatic mitochondria obtained from rats placed on a 1% hydrazine diet for 3 days became slightly enlarged and sometimes elongated, while they became gigantic after 7 days of hydrazine intoxication. Changes were observed in mitochondria from rats treated with hydrazine for 3 days. Total amounts of phospholipids extracted from mitochondria and submitochondrial fractions were increased. Among phospholipid species, relative amounts of acidic phospholipids were increased. Contents of Ca2+ in mitochondria were increased. Differential scanning calorimetric analysis of mitochondria, especially that of the outer membrane fraction, showed that the thermotropic lipid phase transition temperatures were elevated accompanying the broadening of thermograms and the increase in transition enthalpy. Contents of water in mitochondria were increased significantly with the ratio of freezable water to unfreezable water unchanged. Among the changes observed was that the total amount of phospholipids (except for that of the outer membrane fraction) and the contents of water and Ca2+ nearly returned to normal in megamitochondria after 7 days of hydrazine intoxication. Relative amounts of phospholipids and thermotropic lipid phase transition temperatures of megamitochondria did not return to normal levels and yet changes were smaller than those obtained from 3 days of hydrazine intoxication. The fluidity of mitochondrial membranes was not affected by hydrazine treatment. These data would suggest that hydrazine-induced megamitochondrial formation is not due simply to the swelling of mitochondria, but might be due to the fusion of adjacent mitochondria by Ca2+-acidic phospholipid interactions, and once megamitochondria are formed the mitochondrial membranes are stabilized. |
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