The role of stomatin-like protein (STOML) in Plasmodium falciparum

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 has been shown to be essential and to localize to puncta on mitochondrial branching points in oocyst stages. In this study, we investigate the function of STOML in the human malaria parasite, P. falciparum . We show that deletion of STOML causes a significant growth defect and slower asexual blood-stage (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 AlphaFold structure of STOML shows high similarity with the bacterial HflK/C, which has been shown to form a large vault like structure around the bacterial FtsH hexamers. Combined, our results suggest that a similar STOML-FtsH complex localized to specific loci of P. falciparum mitochondria facilitate the parasite’s asexual blood-stage development.