Building without the architect: the dispensable role of MICOS in de novo cristae formation in malaria parasites

Tassan-Lugrezin, S.; Bregy, I.; Lopez Orra, J.; Proellochs, N. I.; van Gemert, G.-J.; Stoter, R.; Evers, F.; Kooij, T. W. A.; van Niftrik, L.

doi:10.1101/2025.10.13.682069

bioRxiv · 10.1101/2025.10.13.682069

Building without the architect: the dispensable role of MICOS in de novo cristae formation in malaria parasites

Tassan-Lugrezin, S.·Bregy, I.·Lopez Orra, J.·Proellochs, N. I.·van Gemert, G.-J.·Stoter, R.·Evers, F.·Kooij, T. W. A.·van Niftrik, L.

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Abstract

The malaria parasite mitochondria represent the only tractable, naturally occurring system in which cristae, the characteristic invaginations of the inner mitochondrial membrane, are known to be formed de novo. In traditional model organisms, the central complex involved in cristae organization is the mitochondrial contact site and cristae organizing system (MICOS). However, whether MICOS has an active role in the initial formation of cristae remains unclear. We identified two putative Plasmodium falciparum MICOS components, PfMIC19 and PfMIC60 and show that both genes are dispensable in asexual blood stages, gametocytes, and mosquito stages, albeit with a mild reduction in oocyst numbers. Immunofluorescence microscopy and electron tomography of gametocytes lacking either or both MICOS orthologues showed aberrant mitochondrial morphology and abnormal cristae, with a marked reduction of crista junctions. Thus, by utilizing the unique properties of P. falciparum, we confirmed the involvement of PfMIC19 and PfMIC60 in the organization of crista junctions, while providing evidence that MICOS is not required for the initial formation of cristae.

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Tassan-Lugrezin, S., Bregy, I., Lopez Orra, J., Proellochs, N. I., van Gemert, G.-J., Stoter, R., Evers, F., Kooij, T. W. A., van Niftrik, L.. 2025-10-13. Building without the architect: the dispensable role of MICOS in de novo cristae formation in malaria parasites. https://doi.org/10.1101/2025.10.13.682069

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