Role of lipid transfer proteins in the abnormal lipid content of Morris hepatoma mitochondria and microsomes.

The level of nonspecific lipid transfer protein in three Morris hepatomas of varying degrees of differentiation has been found to be less than 10% of the level in either host or control livers, whereas phosphatidylcholine transfer activity is slightly reduced for hepatomas compared to host livers (20 to 40%), though nearly the same as levels present in livers of non-tumor-bearing rats. Two major differences have been observed in the lipid compositions of tumor mitochondrial and microsomal membranes compared to those of normal membranes. For all three hepatomas, the cholesterol content of mitochondria is markedly elevated, and the phospholipid content of microsomes is reduced (per mg of protein). As a consequence of the above alterations, the cholesterol: phospholipid ratio of both the microsomal and mitochondrial membranes of these tumors is increased, and the extent of this increase correlates well with the degree of differentiation of the hepatomas. If an important physiological role of lipid transfer proteins is to transfer newly synthesized lipids from microsomes to other cellular organelles, one would expect a 10-fold decline of nonspecific lipid transfer protein activity in hepatomas to result in phospholipid and cholesterol accumulation in microsomes and depletion in mitochondria. The observed decline of phospholipid in microsomes and accumulation of cholesterol in mitochondria from hepatomas suggest that this is not an important function of the nonspecific lipid transfer protein. Finally, preliminary studies of the possibility that the elevated cholesterol: phospholipid levels in hepatoma membranes affect the activities of enzymes of these membranes are reported.