Title:Copper Homeostasis for the Developmental Progression of Intraerythrocytic Malarial Parasite
Volume: 16
Issue: 27
Author(s): Hiroko Asahi, Fumie Kobayashi, Shin-Ichi Inoue, Mamoru Niikura, Kenji Yagita and Mohammed Essa Marghany Tolba
Affiliation:
Keywords:
Copper-binding protein, Copper homeostasis, Developmental arrest, Gene expression, Non-esterified fatty acids,
Plasmodium falciparum, Copper ion.
Abstract: Malaria is one of the world’s most devastating diseases, particularly in the
tropics. In humans, Plasmodium falciparum lives mainly within red blood cells, and malaria
pathogenesis depends on the red blood cells being infected with the parasite. Nonesterified
fatty acids (NEFAs), including cis-9-octadecenoic acid, and phospholipids have
been critical for complete parasite growth in serum-free culture, although the efficacy of
NEFAs in sustaining the growth of P. falciparum has varied markedly. Hexadecanoic acid
and trans-9-octadecenoic acid have arrested development of the parasite, in association
with down-regulation of genes encoding copper-binding proteins. Selective removal of
Cu+ ions has blockaded completely the ring–trophozoite–schizont progression of the parasite.
The importance of copper homeostasis for the developmental progression of P. falciparum
has been confirmed by inhibition of copper-binding proteins that regulate copper physiology and function
by associating with copper ions. These data have provided strong evidence for a link between healthy
copper homeostasis and successive developmental progression of P. falciparum. Perturbation of copper homeostasis
may be, thus, instrumental in drug and vaccine development for the malaria medication. We review
the importance of copper homeostasis in the asexual growth of P. falciparum in relation to NEFAs, copperbinding
proteins, apoptosis, mitochondria, and gene expression.
