The evolution, metabolism and functions of the apicoplast

Abstract

The malaria parasite, Plasmodium falciparum, harbours a relict plastid known as the 'apicoplast'. The discovery of the apicoplast ushered in an exciting new prospect for drug development against the parasite. The eubacterial ancestry of the organelle offers a wealth of opportunities for the development of therapeutic interventions. Morphological, biochemical and bioinformatic studies of the apicoplast have further reinforced its 'plant-like' characteristics and potential as a drug target. However, we are still not sure why the apicoplast is essential for the parasite's survival. This review explores the origins and metabolic functions of the apicoplast. In an attempt to decipher the role of the organelle within the parasite we also take a closer look at the transporters decorating the plastid to better understand the metabolic exchanges between the apicoplast and the rest of the parasite cell.

Figure 1.

Morphology of the apicoplast throughout the different life stages of Plasmodium. Images of the malaria parasite at different life stages are taken from Van Dooren et al. (2005), Okamoto et al. (2009) and Stanway et al. (2009). In the intra-erythrocytic stages and the gametocyte. Green denotes mitochondrion; red denotes apicoplast; blue denotes nucleus. In the sporozoite and other non-erythrocytic stages of the parasite, green denotes apicoplast; red denotes mitochondrion; blue denotes nucleus. (Reproduced with permission from Stanway et al. (2009), The Biochemical Society, http://www.biolcell.org).

Figure 2.

Metabolic map of apicoplast in relation to the mitochondrion in Plasmodium. PfoTPT and PfiTPT are the only identified transporters on the apicoplast. They are hypothesized to supply carbon and energy to fuel the metabolic pathways of the organelle. The nature and fates of the substances the apicoplast is predicted to make are unknown, as indicated by the question marks. ALA: aminolaevulinic acid; CPIII: coproporphyrinogen III; DHAP: dihydroxyacetone phosphate; DOXP: 1-deoxy-D-xylulose-5-phosphate; DXS: DOXP synthase; G3P: glycerol-3-phosphate; GA3P: glyceraldehyde-3-phosphate; GpdA: glycerol-3-phosphate dehydrogenase; 3PGA: 3-phosphoglyceric acid; PDH: pyruvate dehydrogenase; PEP: phosphoenolpyruvate; PfiTPT: P. falciparum innermost triose phosphate translocator; PfoTPT: P. falciparum outermost triose phosphate translocator; PK: pyruvate kinase; and TPI: triose phosphate isomerase.