A ubiquinone-biosynthesis microdomain, not bulk Q supply, is required for succinate dehydrogenase in Toxoplasma that lacks Complex I

Verdict. Toxoplasma gondii has no Complex I, and it wires ubiquinone biosynthesis directly to succinate dehydrogenase. Knocking down TgCoq4 kills SDH activity, extra ubiquinone does not bring it back, and succinate over-reduces the Q pool. The quinone is local, not a freely mixing pool you can spike in from the medium.

Metal sites and redox

The couple the authors actually invoke is ubiquinone/ubiquinol (Q/QH2). Succinate over-reduces that pool and limits further electron flow, with ROS data offered as support. Canonical mitochondrial SDH carries FAD, a [2Fe-2S], a [4Fe-4S], a [3Fe-4S], and heme b. Canonical Complex III carries a Rieske [2Fe-2S] and b and c1 hemes. This abstract does not name those clusters or hemes, and it does not report a core oxidation level. Do not treat textbook SDH Fe-S composition as a measured result. TMPD/ascorbate feeds cytochrome c / Complex IV, which still uncoupler-stimulates, so the block is on the succinate-to-Q path, not a dead terminal oxidase. Malate-supported respiration also reaches capacity, so some other dehydrogenase can still reduce a functional downstream chain. The missing piece is efficient succinate oxidation when UQ synthesis is locally disrupted.

What the authors report

Complex I is the usual NADH entry and a redox-regulation site in most eukaryotes. Apicomplexan parasites, including T. gondii, lack it. The authors identify a parasite-specific mitochondrial microdomain that physically and functionally couples UQ biosynthesis to SDH. Proximity labeling, membrane yeast two-hybrid, reciprocal co-immunoprecipitation, and blue native PAGE show UQ-biosynthesis proteins associating with parasite-specific SDH subunits and co-migrating as a high-molecular-weight assembly. Knockdown of TgCoq4, a UQ-biosynthesis component, reduced SDH activity. Adding exogenous UQ to the assay did not restore it, so UQ availability in bulk is not sufficient for efficient succinate oxidation. FCCP stimulates malate- and TMPD/ascorbate-supported respiration to maximal capacity but fails to do so with succinate. Together with ROS data, that pattern argues that succinate over-reduces the UQ pool and limits further electron flow. Complex III also associates with the UQ-synthesis machinery, suggesting a larger assembly. UQ biosynthesis and electron transport are physically and functionally integrated in a mitochondrion that has no Complex I.

What was measured

Proximity and physical association of UQ-synthesis proteins with parasite-specific SDH subunits, co-migration on blue native PAGE, TgCoq4 knockdown, SDH activity plus or minus exogenous UQ, uncoupler-stimulated respiration on malate, succinate, and TMPD/ascorbate, ROS, and CIII association with the UQ-synthesis machinery.

Caveats

Abstract only. Preprint. Exogenous UQ form, concentration, and delivery are unnamed. Fe-S nuclearity is not reported. Whether this microdomain is shared across Apicomplexa is open.

What to do with it

Treat T. gondii succinate oxidation as a biosynthesis-SDH-CIII microdomain problem, not as a missing bulk quinone. The molecular test is whether restoring TgCoq4 at the assembly, rather than flooding UQ, recovers SDH activity and relieves Q-pool over-reduction on succinate.

Bibliographic record

Abstract-based editorial synthesis by Mitos. Not peer review.