SDHB

TgSdhB is a validated iron-sulfur subunit of the Toxoplasma gondii succinate dehydrogenase (complex II), first assigned to complex II by complexome profiling showing co-migration with other SDH subunits (PMID:33651838) and confirmed as an integral catalytic-core component whose integrity is required for SDH assembly and enzymatic activity (PMID:38079448). Disruption of TgSdhB impairs mitochondrial respiration and triggers spontaneous bradyzoite differentiation, linking complex II function to suppression of stage conversion (PMID:38079448). Unlike canonical eukaryotic SDH, membrane attachment of the TgSdhA/TgSdhB catalytic core depends on the myzozoan-specific membrane protein TgMPODD; depletion of TgMPODD detaches TgSdhA/TgSdhB from the membrane anchor and abolishes SDH activity (PMID:38835243).

1. 2021 Medium

   Establishing which mitochondrial complex TgSdhB belongs to was the first step, resolving its compositional assignment within the Toxoplasma electron transport chain.

   Evidence complexome profiling (native gel electrophoresis coupled with mass spectrometry) of Toxoplasma mitochondria

   PMID:33651838

   Open questions at the time

   • co-migration is compositional, not functional, evidence
   • does not establish catalytic contribution or membrane-anchoring architecture
2. 2023 High

   Moving from compositional assignment to function, loss-of-function experiments established that TgSdhB integrity is required for SDH assembly, enzymatic activity, respiration, and suppression of bradyzoite differentiation.

   Evidence conditional genetic disruption with SDH activity assays, respiration measurements, and differentiation assays in T. gondii

   PMID:38079448

   Open questions at the time

   • does not resolve how the catalytic core attaches to the inner mitochondrial membrane
   • molecular basis of the differentiation phenotype not defined
3. 2024 High

   Addressing the atypical architecture of the parasite complex, TgMPODD was identified as the lineage-specific membrane anchor tethering the TgSdhA/TgSdhB core to the inner mitochondrial membrane, explaining SDH membrane attachment in the absence of canonical SdhC/SdhD.

   Evidence co-immunoprecipitation, BioID-type proximity assays, conditional knockdown of TgMPODD, membrane fractionation, SDH activity and O2 consumption measurements

   PMID:38835243

   Open questions at the time

   • structural model of the anchored complex not determined
   • stoichiometry of the myzozoan-specific subunits not resolved

• The molecular mechanism linking loss of SDH/complex II activity to spontaneous bradyzoite differentiation remains unresolved.
• no signaling pathway connecting respiratory defect to stage conversion identified
• no structural characterization of TgSdhB or the assembled parasite complex II