Metabolic dependency of ribosome heterogeneity in the human malaria parasite

To infect new hosts, the human malaria parasite Plasmodium falciparum needs to transmit to a mosquito vector. One of the most compelling adaptations to the two different host environments is the transcription of divergent ribosomal RNA genes that are transcribed from distinct genomic loci. Here we show that the silencing of mosquito-stage specific rRNA transcription is coupled to the level of aerobic glycolysis, the parasites premier metabolic pathway in the human host. We show that NAD+ levels originating from lactate fermentation are translated on a molecular level by the histone deacetylase Sir2a. By comprehensively characterizing histone epigenetic modifications in Sir2a-KO and wild-type cells coupled with quantitative chromatin immunoprecipitation, we show that the parasite metabolic state is linked to a functional transcriptional output.