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Cited by 6Malaria Research and ControlMitochondrial Function and PathologyHeat shock proteins research

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Plasmodium falciparum stomatin-like protein forms a putative complex with a metalloprotease in distinct mitochondrial loci

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Verhoef, Julie M.J., Bekkering, Ezra T., Boshoven, Cas, Hannon, Megan, Evers, Felix, Proellochs, Nicholas I., Spruijt, Cornelia G., Kooij, Taco W. A.·2026·PLOS Pathogens
DOI 10.1371/journal.ppat.1013922PMC PMC12912694

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Abstract

Members of the S tomatin, P rohibitin, F lotillin and H flK/C (SPFH) protein family form large membrane anchored or spanning complexes and are involved in various functions in different organelles. The human malaria causing parasite Plasmodium falciparum harbors four SPFH proteins, including prohibitin 1 and 2, prohibitin-like protein (PHBL), and stomatin-like protein (STOML), which all localize to the parasite mitochondrion. In the murine model parasite Plasmodium berghei , STOML appears essential for asexual blood-stage (ABS) development and is localized to puncta on mitochondrial branching points in oocyst stages. In this study, we show that deletion of P. falciparum STOML causes a significant growth defect and slower ABS development, while sexual-stage development remains unaffected. Parasites lacking STOML were not more sensitive to respiratory chain targeting drugs, rendering a function of STOML in respiratory chain assembly unlikely. Epitope tagging of endogenous STOML revealed a distinct punctate localization on branching points and endings of the ABS mitochondrial network. STOML resides in a large protein complex and pulldown experiments identified a zinc dependent metalloprotease, FtsH, as a likely interaction partner. The predicted AlphaFold2 structure of STOML shows high similarity with the bacterial HflK/C, which has been shown to form a large vault-like structure around bacterial FtsH hexamers. Combined, our results suggest that a similar STOML-FtsH complex localized to specific loci of P. falciparum mitochondria facilitates the parasite’s ABS development.

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Metadata

Authors
Verhoef, J. M. J., Bekkering, E. T., Boshoven, C., Hannon, M., Evers, F., Proellochs, N. I., Spruijt, C. G., & Kooij, T. W. A.
Affiliations
  • Radboud University Medical Center (NL)
  • Radboud University Nijmegen (NL)
Corresponding author
Kooij, Taco W. A.
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2026-02-09
Volume
22
Issue
2
Pages
e1013922
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1013922
PMC
PMC12912694
OpenAlex
W7128421337
Cited by
6
References
2
Citations by year
2026: 3
FWCI
19.21
Type
journal article
Language
en
Update notices
new_version (2026-02-17)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Netherlands Organisation for Scientific Research (NWO-VIDI864.13.009)
  • Radboud Universitair Medisch Centrum (Masters round 2018, Masters round 2021)
  • Radboud University Medical Center (RIMLS018-009b)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
Plasmodium falciparum, prohibitin, mitochondrial protein complexes, asexual blood stage development, respiratory chain assembly
MeSH terms
Animals, Humans, Membrane Proteins, Mitochondria, Plasmodium berghei, Plasmodium falciparum, Protozoan Proteins, Metalloproteases, Mice

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