Inheritance of the genome-less apicoplast in the 'apicoplast-minus' Plasmodium falciparum

Abstract

Most apicomplexan parasites contain a plastid-derived organelle called the apicoplast, which originated through secondary endosymbiosis. As a result of this evolutionary trajectory, the non-photosynthetic apicoplast is surrounded by four membranes and contains many bacterial-like, druggable targets. It is widely accepted that asexual malaria parasites (Plasmodium falciparum) can thrive under antibiotic treatment if supplemented with high concentrations of isopentenyl pyrophosphate (IPP, 200 {micro}M) and these IPP-rescued parasites are thought to lack the apicoplast and its 35 kb genome but possess many vesicles. However, our findings challenge this apicoplast-minus concept. In late-stage schizonts, we observed that the apicoplast-derived vesicles nearly colocalize with mitochondria and are properly distributed into merozoites during schizogony, suggesting that they are inherited rather than newly synthesized in each asexual cycle. Further, immuno-electron microscopy (immuno-EM) revealed that the "apicoplast-minus" parasites possess structures surrounded by four membranes, in addition to single-membrane-surrounded entities. The presence of four-membrane-bound structures suggests that the apicoplast has not truly disappeared in the "apicoplast-minus" P. falciparum but remains in a distinct, diminished form. We termed this genome-less apicoplast derivative the apicosome, drawing an analogy to the genome-less mitochondrial derivative known as the mitosome. We propose that apicosomes retain essential biochemical and/or structural functions, which act as barriers to the complete loss of apicoplast when the parasites face antibiotic stress and IPP rescue.