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 μM) 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.