An essential role for an Fe-S cluster protein in the cytochrome c oxidase complex of Toxoplasma parasites

Rachel A. Leonard, Yuan Tian, Feng Tan, Giel G. van Dooren, Jenni A. Hayward

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The mitochondrial electron transport chain (ETC) of apicomplexan parasites differs considerably from the ETC of the animals that these parasites infect, and is the target of numerous anti-parasitic drugs. The cytochrome c oxidase complex (Complex IV) of the apicomplexan Toxoplasma gondii ETC is more than twice the mass and contains subunits not found in human Complex IV, including a 13 kDa protein termed TgApiCox13. TgApiCox13 is homologous to a human iron-sulfur (Fe-S) cluster-containing protein called the mitochondrial inner NEET protein (HsMiNT) which is not a component of Complex IV in humans. Here, we establish that TgApiCox13 is a critical component of Complex IV in T. gondii, required for complex activity and stability. Furthermore, we demonstrate that TgApiCox13, like its human homolog, binds two Fe-S clusters. We show that the Fe-S clusters of TgApiCox13 are critical for ETC function, having an essential role in mediating Complex IV integrity. Our study provides the first functional characterisation of an Fe-S protein in Complex IV.

Original languageEnglish
Article numbere1011430
Number of pages39
JournalPLoS Pathogens
Issue number6
Publication statusPublished - 1 Jun 2023
Externally publishedYes

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