J. Biol. Chem., Vol. 255, Issue 22, 10566-10568, 11, 1980
cis-Unsaturated fatty acids inhibit cap formation on lymphocytes by depleting cellular ATP
AN Corps, T Pozzan, TR Hesketh and JC Metacalfe
The inhibition of anti-immunoglobulin cap formation on lymphocytes by
cis-unsaturated fatty acids, but not saturated or trans-unsaturated fatty
acids, which recently been reported (Klausner, R. N., Bhalla, D. K.,
Dragsten, P., Hoover, R. L., and Karnovsky, M. J. (1980) Proc. Natl. Acad.
Sci. U. S. A. 77, 437-441), can be accounted for quantitatively by the
effects of the fatty acids on ATP levels in the intact cells. Only the
cis-unsaturated fatty acids lowered the cellular ATP level sufficiently (to
< 80%) to inhibit cap formation significantly. The profile for the
dependence of cap formation on cellular ATP level obtained with the fatty
acids is very similar to the corresponding profile described previously for
several capping ligands and a range of metabolic inhibitors used to depress
the cellular ATP levels. Oxygen electrode experiments indicate that the
unsaturated, but not the saturated, fatty acids can uncouple lymphocyte
mitochondria in intact cells, whereas both types of fatty acids can
uncouple isolated rat liver mitochondria. The difference in the effect of
the two types of fatty acids on ATP levels in the intact cells is
attributed to the inability of the saturated fatty acids to penetrate in
sufficient concentrations to the mitochondria to cause uncoupling. The
protective action of external calcium against inhibition of capping by the
free fatty acids is attributed to the effect of calcium in cross-bridging
the anionic fatty acids and reducing their effective concentration. These
interpretations account for all of the experimental data and are much
simpler than the model proposed by Klausner et al.