# Plasmodium ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger complex

## TL;DR

This study shows that the malaria parasite uses a unique Aurora kinase complex to control cell division, which is essential for its survival and transmission.

## Contribution

The study identifies a non-canonical chromosomal passenger complex in Plasmodium involving ARK1 and divergent INCENPs.

## Key findings

- ARK1 is essential for spindle formation and mitotic progression in Plasmodium.
- ARK1 forms a chromosomal passenger complex with divergent INCENPs, lacking canonical subunits.
- Disruption of ARK1 affects parasite transmission and cell division stages.

## Abstract

Mitosis in Plasmodium spp., the causative agent of malaria, is fundamentally different from model eukaryotes, proceeding via a bipartite microtubule organising centre (MTOC) and lacking canonical regulators such as Polo kinases. During schizogony, asynchronous nuclear replication produces a multinucleate schizont, while rapid male gametogony generates an octaploid nucleus before gamete formation. Here, we identify Aurora-related kinase 1 (ARK1) as a key component of inner MTOC and spindle formation, controlling kinetochore dynamics and driving mitotic progression. Conditional ARK1 depletion disrupts spindle biogenesis, kinetochore segregation, karyokinesis and cytokinesis in both stages, and affects parasite transmission. Interactome analysis shows that ARK1 forms the catalytic core of a non-canonical chromosomal passenger complex (CPC) containing two highly divergent inner centromere proteins (INCENPs), which we term INCENP-A and INCENP-B, and lacking the canonical chromatin-targeting subunits Survivin and Borealin. Comparative genomics suggests that apicomplexan INCENPs arose through recurrent lineage-specific duplications, reflecting an evolutionary rewiring of CPC architecture in this eukaryotic lineage. Together, these findings reveal key adaptations in Plasmodium mitosis involving ARK1 and its INCENP scaffolds, and identify the ARK1–INCENP interface as a potential multistage target for antimalarial intervention.

This study reveals that the malaria parasite Plasmodium uses a unique Aurora kinase complex to control cell division. This divergent machinery regulates spindle formation and is essential for parasite transmission.