NUP503

TgNup503 is a nuclear pore component in Toxoplasma gondii that functions as a molecular tether establishing a nuclear-mitochondrial membrane contact site through physical interaction with the mitochondrial protein translocon component TgTom40 (PMID:38456969). Genetic depletion of TgNup503 reduces these contact sites and produces mitochondrial morphology and functional defects, implicating TgNup503-mediated contacts in nuclear-mitochondrial organelle communication (PMID:38456969). Beyond this tethering and organelle-communication role, no further mechanistic detail has been characterized in the available corpus.

1. 2024 Medium

   Whether a nuclear pore component physically bridges the nucleus and mitochondrion was unknown; identifying a reciprocal interaction between TgNup503 and the TOM translocon component TgTom40 established a defined molecular tether at a nuclear-mitochondrial membrane contact site.

   Evidence Co-IP/interaction assay between nuclear pore and TOM translocon components plus genetic disruption showing contact site reduction, in Toxoplasma gondii

   PMID:38456969

   Open questions at the time

   • The interaction interface and whether binding is direct versus bridged by additional factors is not resolved
   • No structural model of the contact site is available
   • Stoichiometry and dynamics of the tether are uncharacterized
2. 2024 Medium

   Whether these contact sites are functionally important was unknown; conditional depletion of TgNup503 causing mitochondrial morphology and functional defects established that the tether mediates nuclear-mitochondrial organelle communication.

   Evidence Conditional depletion/knockdown of TgNup503 with mitochondrial morphology and function readouts in Toxoplasma gondii

   PMID:38456969

   Open questions at the time

   • The molecular content exchanged across the contact site is not identified
   • Mechanism linking loss of contact to mitochondrial functional decline is unresolved
   • Whether the phenotype reflects loss of tethering versus a separate nuclear pore function is not distinguished

• What molecules or signals are transmitted across the TgNup503-TgTom40 contact site, and the structural basis of the tether, remain unknown.
• No cargo or signal transferred across the contact site identified
• No structural characterization of the tether
• Regulation of contact site formation is uncharacterized