Mitochondrial electron transport chain of Plasmodium species (null)

The mitochondrial electron transport chain of Plasmodium species is an essential multi-enzyme system located in the inner mitochondrial membrane, performing two key roles: providing electrons required for pyrimidine biosynthesis (mainly via supporting dihydroorotate dehydrogenase activity) and generating a transmembrane proton gradient that can be used for ATP synthesis, especially during transmission stages[1][3][7]. Structurally, it includes a type II NADH dehydrogenase (NDH2), malate:quinone oxidoreductase (MQO), succinate dehydrogenase (Complex II), cytochrome bc1 complex (Complex III), cytochrome c, and cytochrome c oxidase (Complex IV), with significant differences compared to the mammalian ETC that provide selective drug targeting opportunities[1][7]. It is validated as a critical antimalarial drug target, with several clinically used (e.g., atovaquone, proguanil) and investigational compounds specifically inhibiting its components, particularly Complex III and DHODH[6][8][10]. Resistance can arise via mutations, especially in cytochrome b, and combination therapies are commonly used to address this challenge.

Other names

Mitochondrial electron transport chain (mtETC)mETCElectron transport chain (ETC) of PlasmodiumPlasmodium mitochondrial ETC

Inhibition of cytochrome bc1 complex (prevents electron transfer and ubiquinone recycling)[3][6][7]; Inhibition of DHODH (blocks pyrimidine biosynthesis)[1][8]; Disruption of proton gradient/electrochemical membrane potential[3][6]; Collapse of mitochondrial membrane potential (especially with atovaquone + proguanil)[3]