Characterizing the cryptic stator of the Toxoplasma ATP synthase

Orateur : Diego HUET (Whitehead Institute for Biomedical Research, Boston, USA)

The mitochondrial ATP synthase is a macromolecular complex highly conserve across living organisms. The two portions of the complex (F1 and Fo) work together by coupling proton flux through the Fo sector to conformational changes in F1, where synthesis of ATP takes place. Proper function of the synthase requires the rotational torque of F1 to be counteracted by the stator portion of Fo, yet sequence-based searches in apicomplexans fail to identify genes encoding several key elements of the stator. We previously identified several mitochondriallylocalized proteins, unique to apicomplexans, and essential for survival of Toxoplasma in human fibroblasts. Interestingly, the secondary structure of one such protein (ICAP2), resembled that of the ATP synthase b subunit, one of the missing apicomplexan stator components. Coimmunoprecipitation showed that ICAP2 interacts with all the known ATP synthase subunits, consistent with its putative role as a stator element. Moreover, several other ICAPs seem to interact with the ATP synthase including ICAP8, one of the mitochondrially-localized proteins from our screen, and a novel ICAP that seems to possess structural similarity to the d subunit of the stator. By generating a conditional knockdown of ICAP2, we confirm its essential function in T. gondii. Intriguingly, depletion of ICAP2 caused aberrant mitochondrial morphology. These findings will reveal new information regarding the unconventional apicomplexan stator. The function of the ATP synthase appears to vary throughout the life cycles and evolution of apicomplexan parasites, making it an intriguing lens through which to view the adaptation of the phylum.

Télécharger dans mon agenda