Chloroquine-induced Masking of a Lipid That Promotes Ferriprotoporphyrin IX Dimerization in Malaria

Abstract Mice infected with the NYU-2 strain of Plasmodium berghei were used to study the effect of chloroquine on masking of a lipid that promotes ferriprotoporphyrin IX dimerization. More than 40% of this lipid was masked and unable to promote dimerization in membrane ghosts from erythrocytes of untreated, infected mice. Thus, preparations of membrane ghosts dimerized 57 ± 6 nmol of ferriprotoporphyrin IX during a 2-h incubation, whereas the lipids extracted from these preparations dimerized 101 ± 11 nmol of ferriprotoporphyrin IX (means ± S.D. for four experiments). Exposure of membrane ghosts to sonication or cold significantly increased the extent of masking. In addition, chloroquine treatment of infected mice increased the extent of masking to ∼90%. The lipid could be unmasked by extracting it into acetone or by aging erythrocyte membrane ghosts from untreated or chloroquine-treated, infected mice for 24 h at pH 7.4 and 25 °C. These findings indicate that masking and unmasking of a lipid is central to the regulation of ferriprotoporphyrin IX dimerization in malaria parasites. They also indicate that chloroquine impairs the function of this regulatory process.