STOML

PF3D7_0318100 (STOML) is a mitochondrion-localized SPFH-family stomatin-like protein of Plasmodium falciparum that functions in asexual blood-stage (ABS) development (PMID:41662436). Endogenous epitope tagging places STOML at discrete puncta on branching points and endings of the ABS mitochondrial network rather than uniformly across the organelle (PMID:41662436), and stage-specific expression analysis shows it is present in trophozoites but not rings (PMID:12905716). Genetic deletion of STOML causes a significant growth defect and slowed ABS development while leaving sexual-stage development intact, defining a role restricted to the asexual cycle (PMID:41662436); knockout parasites are not sensitized to respiratory chain-targeting drugs, arguing against a role in respiratory chain assembly (PMID:41662436). STOML resides in a large protein complex, with pulldown mass spectrometry identifying the zinc-dependent metalloprotease FtsH as a likely partner, and an AlphaFold2 model resembling bacterial HflK/C — which forms a vault-like assembly around FtsH hexamers — points to an analogous STOML–FtsH mitochondrial complex (PMID:41662436). Beyond this complex membership and localization, the precise molecular activity of STOML has not been characterized in the available corpus.

1. 2003 Low

   Establishing when STOML is expressed during the erythrocytic cycle was the first step toward defining its cellular context.

   Evidence RT-PCR cloning, prokaryotic expression and Western blot of a recombinant C-terminal fragment in P. falciparum FCC1/HN

   PMID:12905716

   Open questions at the time

   • No localization determined
   • No functional role assigned
   • Antigen detected only via recombinant fragment, not endogenous protein
2. 2018 Low

   Whether the stomatin-like protein resides in the mitochondrion and is required for blood-stage growth was addressed in a rodent malaria model.

   Evidence Fluorescence microscopy localization and attempted gene deletion in P. berghei

   PMID:29669282

   Open questions at the time

   • Essentiality inferred indirectly from failed deletion, not from a conditional system
   • Species is P. berghei, not the subject P. falciparum gene
   • Sub-mitochondrial localization not resolved
3. 2026 Medium

   The sub-organellar position and stage-specific requirement of P. falciparum STOML were resolved, establishing a defined ABS-restricted role.

   Evidence Endogenous epitope tagging with fluorescence microscopy and genetic deletion with growth/developmental readout in P. falciparum

   PMID:41662436

   Open questions at the time

   • Molecular reason for punctate localization at network branch points unknown
   • Mechanism linking loss of STOML to slowed asexual development not defined
4. 2026 Low

   Whether STOML acts alone or within a complex, and whether it participates in respiratory chain assembly, was tested to narrow its molecular function.

   Evidence Pulldown/co-IP mass spectrometry, AlphaFold2 structural prediction, and drug-sensitivity assay on STOML-knockout P. falciparum

   PMID:41662436

   Open questions at the time

   • FtsH interaction from a single pulldown without reciprocal validation, mutagenesis, or reconstitution
   • HflK/C-like architecture is computational prediction only, no experimental structure
   • Functional consequence of the STOML–FtsH complex undetermined

• The biochemical activity of STOML within the proposed FtsH complex and how it contributes to asexual blood-stage growth remain unresolved.
• No demonstrated enzymatic or scaffolding activity
• Stoichiometry and architecture of the STOML–FtsH assembly not experimentally determined
• Mechanistic basis of the growth defect not established