ALTERATION OF MITOCHONDRIAL-FUNCTION AND LIPID-COMPOSITION IN MORRIS-7777 HEPATOMA

  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (9) , 3246-3254
Abstract
Mitochondria isolated from the [rat] Morris hepatoma 7777 demonstrated a different phospholipid composition from those of control mitochondria, with respect to the amounts of the various types present and fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, whereas there was an increase in the level of monounsaturated fatty acids. The usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids. A high percentage of monounsaturated fatty acid was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% vs. 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per molecule than those from liver mitochondria. The .zeta. potential of liposomes of the hepatoma phospholpids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. Ca stimulated phospholipase A activity of hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. Maximal activity was lower, than that noted in liver mitochondria. By following the incorporation of [3H]ethanolamine into mitochondrial phospholipids, the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of the endoplasmic reticulum and mitochondrion. Accompanying the changes in phospholipid composition and metabolism were alterations in mitochondrial energy linked processes. Hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1 mM EDTA and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration.