ALV12

ALV12 (IMC10) is an alveolin-domain protein of the Toxoplasma gondii inner membrane complex (IMC) that functions as a structural tether coordinating mitochondrial morphology and inheritance with the parasite pellicle (PMID:36314270). IMC10 localizes to the IMC and physically interacts with the outer mitochondrial membrane-associated protein LMF1, and this interaction defines a membrane tether linking the mitochondrion to the IMC (PMID:36314270). Conditional depletion of IMC10 does not compromise parasite viability but severely disrupts mitochondrial morphology and impairs distribution of the mitochondrion to daughter cells during division, phenocopying loss of its partner LMF1 and establishing the LMF1/IMC10 complex as part of the machinery governing mitochondrial inheritance (PMID:36314270, PMID:39374269). Beyond its role in this tethering complex, nothing further about ALV12 has been characterized in the available corpus.

1. 2022 Medium

   Identified how the Toxoplasma mitochondrion is physically anchored to the pellicle by establishing ALV12/IMC10 as an IMC-resident binding partner of the outer mitochondrial membrane protein LMF1, defining a novel mitochondrion-IMC tether.

   Evidence Yeast two-hybrid screen with orthogonal pulldown/Co-IP confirmation in T. gondii

   PMID:36314270

   Open questions at the time

   • Interaction interface / alveolin domain requirement not mapped
   • Whether the interaction is direct or bridged by additional factors not resolved
2. 2022 Medium

   Tested the functional consequence of the tether by showing that conditional loss of ALV12/IMC10 disrupts mitochondrial morphology and inheritance without killing the parasite, establishing the tether as required for mitochondrial positioning rather than for survival.

   Evidence Inducible conditional knockdown with fluorescence imaging of mitochondrial morphology and inheritance in T. gondii

   PMID:36314270

   Open questions at the time

   • Molecular mechanism linking tether loss to morphology defect unresolved
   • Residual mitochondrial function in depleted parasites not quantified
3. 2024 Medium

   Corroborated the LMF1/IMC10 complex as part of the machinery governing mitochondrial morphology and inheritance, with high-resolution imaging confirming defective inheritance to daughter buds upon IMC10 loss.

   Evidence Conditional knockdown plus ultrastructure expansion microscopy (U-ExM) and fluorescence imaging in T. gondii

   PMID:39374269

   Open questions at the time

   • Full protein composition of the tethering machinery not defined
   • Spatiotemporal regulation of tether assembly during division not resolved