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

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 and Bub1 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 reveals ARK1 as the catalytic core of a non- canonical chromosomal passenger complex (CPC) containing two divergent inner centromere proteins (INCENPs) but lacking Survivin and Borealin. Comparative genomics indicates this CPC architecture arose early in Apicomplexa, replacing canonical centromere-targeting modules. These findings uncover a distinct mitotic machinery in Plasmodium and identify the ARK1–INCENP interface as a potential multistage target for malaria therapeutic intervention.

疟原虫属（Plasmodium spp.，疟疾的致病原）的有丝分裂与模式真核生物存在本质差异，其通过双分体微管组织中心（microtubule organising centre, MTOC）完成分裂过程，且缺乏Polo激酶、Bub1激酶等经典调控因子。在裂殖生殖阶段，异步化的核复制会产生多核裂殖体；而快速的雄配子生殖则会在配子形成前生成八倍体核。本研究鉴定出极光相关激酶1（Aurora-related kinase 1, ARK1）为内层MTOC与纺锤体形成的关键组分，其可调控动粒动力学并推动有丝分裂进程。条件性ARK1敲除会破坏两个阶段的纺锤体生物发生、动粒分离、核分裂与胞质分裂，并影响疟原虫的传播。相互作用组分析显示，ARK1是非经典染色体乘客复合体（chromosomal passenger complex, CPC）的催化核心，该复合体包含两种变异的内着丝粒蛋白（inner centromere proteins, INCENPs），但缺乏Survivin与Borealin。比较基因组学分析表明，这种染色体乘客复合体的结构在顶复门（Apicomplexa）早期就已出现，取代了经典的着丝粒靶向模块。这些发现揭示了疟原虫中独特的有丝分裂机制，并确定ARK1-INCENP相互作用界面可作为疟疾治疗干预的潜在多阶段靶点。