Centre for Research in Agricultural Genomics (CRAG), CSIC-IRTA-UAB-UB, Bellaterra 08193, Spain.
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Barcelona 08028, Spain.
Plant Cell. 2023 Sep 1;35(9):3325-3344. doi: 10.1093/plcell/koad172.
Stress granules (SGs) are highly conserved cytoplasmic condensates that assemble in response to stress and contribute to maintaining protein homeostasis. These membraneless organelles are dynamic, disassembling once the stress is no longer present. Persistence of SGs due to mutations or chronic stress has been often related to age-dependent protein-misfolding diseases in animals. Here, we find that the metacaspase MC1 is dynamically recruited into SGs upon proteotoxic stress in Arabidopsis (Arabidopsis thaliana). Two predicted disordered regions, the prodomain and the 360 loop, mediate MC1 recruitment to and release from SGs. Importantly, we show that MC1 has the capacity to clear toxic protein aggregates in vivo and in vitro, acting as a disaggregase. Finally, we demonstrate that overexpressing MC1 delays senescence and this phenotype is dependent on the presence of the 360 loop and an intact catalytic domain. Together, our data indicate that MC1 regulates senescence through its recruitment into SGs and this function could potentially be linked to its remarkable protein aggregate-clearing activity.
应激颗粒（SGs）是高度保守的细胞质凝聚物，可响应应激而组装，并有助于维持蛋白质内稳。这些无膜细胞器是动态的，一旦应激不再存在，它们就会解体。由于突变或慢性应激导致 SGs 的持续存在，常常与动物中与年龄相关的蛋白质错误折叠疾病有关。在这里，我们发现，在拟南芥（Arabidopsis thaliana）受到蛋白毒性应激时，介体型半胱氨酸蛋白酶 MC1 会被动态募集到 SGs 中。两个预测的无序区域，即前导区和 360 环，介导 MC1 被募集到 SGs 中和从 SGs 中释放。重要的是，我们表明 MC1 具有在体内和体外清除有毒蛋白质聚集体的能力，起到了一种解聚酶的作用。最后，我们证明了过表达 MC1 会延迟衰老，并且这种表型依赖于 360 环的存在和完整的催化结构域。总之，我们的数据表明，MC1 通过募集到 SGs 来调节衰老，并且这个功能可能与其显著的蛋白质聚集体清除活性有关。
