Reactive oxygen species-sensitive iron-sulfur cluster proteins and mitochondrial components of Plasmodium spp. (ROS-sensitive Fe-S/Mitochondrial targets)

Reactive oxygen species (ROS)-sensitive iron-sulfur (Fe-S) cluster proteins and mitochondrial components in Plasmodium species represent a critical vulnerability in the malaria parasite's life cycle. These targets include essential enzymes involved in the mitochondrial electron transport chain and pyrimidine biosynthesis, such as dihydroorotate dehydrogenase (DHODH) and various Fe-S cluster-containing proteins that are highly susceptible to oxidative damage. Drugs like artemisinin and its derivatives are thought to exert their potent antimalarial effects by generating ROS that specifically target and deactivate these parasite-specific metabolic hubs. Because Plasmodium relies heavily on its single mitochondrion for pyrimidine synthesis rather than ATP production during the erythrocytic stage, disruption of these components leads to rapid cessation of parasite growth. Understanding the interaction between oxidative stress and these Fe-S clusters is vital for overcoming drug resistance and developing next-generation antimalarials that exploit the parasite's unique redox biology.

Other names

Plasmodium iron-sulfur cluster proteinsMitochondrial respiratory chain complexes of PlasmodiumROS-sensitive malarial proteinsFe-S cluster-containing enzymes in Plasmodium

Induction of oxidative stress leading to the degradation of iron-sulfur clusters and inhibition of mitochondrial electron transport, resulting in metabolic collapse and parasite death.