The apicoplast hosts several essential biosynthetic pathways, nearly all of which rely on reducing power from NADPH. We are currently identifying and characterizing redox systems that maintain NAD(P)H balance in the apicoplast. Disruption of redox balance can impair critical functions such as isoprenoid precursor synthesis and overall organelle integrity. Malaria parasites experience significant oxidative stress from both host immune responses and internal sources like hemoglobin breakdown and mitochondrial metabolism. Unlike antibiotics that cause delayed parasite death, we anticipate that targeting NAD(P)H-dependent processes in the apicoplast will result in rapid parasite clearance by compromising redox homeostasis.

During parasite replication in human red blood cells, mitochondrial activity is markedly reduced. The organelle lacks cristae, and very little oxidative phosphorylation occurs. Nevertheless, the mitochondrion remains essential for the biosynthesis of a few key metabolites like pyrimidines, acetyl-CoA, and iron–sulfur clusters, making it important to study these pathways in detail. We are continuing to characterize these functions and investigating whether the mitochondrion has additional roles during this stage that contribute to parasite survival.