mtRPS18

In P. falciparum, mtRPS18 (PF3D7_1211500) is an essential small-subunit mitoribosomal protein required for mitochondrial function and parasite viability (PMID:32273345). Immuno-electron microscopy localizes mtRPS18 within the mitochondrion, and conditional CRISPR/Cas9 knockdown collapses the mitochondrial membrane potential, blocks pyrimidine biosynthesis by depleting cellular pyrimidine nucleotide pools, and renders parasites hypersensitive to inhibitors of Complex III (bc1), DHODH, and the F1F0-ATP synthase (PMID:32273345). These phenotypes place mtRPS18 alongside the small-subunit proteins PfmtRPS12 and PfmtRPS17 as a component whose loss compromises mitoribosome-dependent maintenance of the electron transport chain (PMID:32273345). Beyond this single characterization (PMID:32273345), no further mechanistic detail on mtRPS18 — including its structural role within the small subunit, direct interaction partners, or the identity of transcripts it helps translate — has been characterized in the available corpus.

1. 2020 Medium

   Whether PF3D7_1211500 is a functional mitoribosomal component essential to the parasite was unknown; conditional knockdown established it as an essential small-subunit protein whose loss cripples mitochondrial energetics and pyrimidine synthesis.

   Evidence CRISPR/Cas9-based conditional knockdown with immuno-EM localization, drug sensitivity assays, and metabolite profiling in P. falciparum

   PMID:32273345

   Open questions at the time

   • No in vitro reconstitution or structural validation of mtRPS18 within the small subunit
   • Direct RNA/protein interaction partners of mtRPS18 not identified
   • Phenotype shared with PfmtRPS12 and PfmtRPS17, so contributions specific to mtRPS18 are not separated

• How mtRPS18 assembles into the mitoribosome and which specific translation events it supports remains unresolved.
• No structural model of mtRPS18 in the small subunit
• Mechanism linking mtRPS18 loss to membrane potential collapse not defined at the molecular level