Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Laboratório de Biomineralização, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Curr Top Membr. 2024;93:27-49. doi: 10.1016/bs.ctm.2024.05.001. Epub 2024 Aug 5.
Malaria remains a major global threat, representing a severe public health problem worldwide. Annually, it is responsible for a high rate of morbidity and mortality in many tropical developing countries where the disease is endemic. The causative agent of malaria, Plasmodium spp., exhibits a complex life cycle, alternating between an invertebrate vector, which transmits the disease, and the vertebrate host. The disease pathology observed in the vertebrate host is attributed to the asexual development of Plasmodium spp. inside the erythrocyte. Once inside the red blood cell, malaria parasites cause extensive changes in the host cell, increasing membrane rigidity and altering its normal discoid shape. Additionally, during their intraerythrocytic development, malaria parasites incorporate and degrade up to 70 % of host cell hemoglobin. This mechanism is essential for parasite development and represents an important drug target. Blocking the steps related to hemoglobin endocytosis or degradation impairs parasite development and can lead to its death. The ultrastructural analysis of hemoglobin endocytosis on Plasmodium spp. has been broadly explored along the years. However, it is only recently that the proteins involved in this process have started to emerge. Here, we will review the most important features related to hemoglobin endocytosis and catabolism on malaria parasites. A special focus will be given to the recent analysis obtained through 3D visualization approaches and to the molecules involved in these mechanisms.
疟疾仍然是一个主要的全球威胁，是全世界严重的公共卫生问题。每年，它在许多疟疾流行的热带发展中国家都导致很高的发病率和死亡率。疟疾的病原体疟原虫表现出复杂的生命周期，在传播疾病的无脊椎动物媒介和脊椎动物宿主之间交替。在脊椎动物宿主中观察到的疾病病理学归因于疟原虫在红细胞内的无性发育。一旦进入红细胞，疟原虫就会引起宿主细胞的广泛变化，增加膜的刚性并改变其正常的盘状形状。此外，在它们的红细胞内发育过程中，疟原虫会掺入并降解多达 70%的宿主细胞血红蛋白。这种机制对寄生虫的发育至关重要，是一个重要的药物靶点。阻断与血红蛋白内吞作用或降解相关的步骤会损害寄生虫的发育并导致其死亡。多年来，人们广泛探索了疟原虫血红蛋白内吞作用的超微结构分析。然而，直到最近，参与这个过程的蛋白质才开始显现出来。在这里，我们将回顾与寄生虫血红蛋白内吞作用和分解代谢相关的最重要特征。特别关注通过 3D 可视化方法获得的最新分析结果以及涉及这些机制的分子。
