Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Diretoria de Extensão, Fundação Centro de Educação a Distância do Cecierj Estado do Rio de Janeiro, Brazil.
Biochim Biophys Acta Mol Basis Dis. 2021 Feb 1;1867(2):166028. doi: 10.1016/j.bbadis.2020.166028. Epub 2020 Nov 25.
Chagas disease is a neglected illness endemic in Latin America that mainly affects rural populations. The etiological agent of Chagas disease is the protozoan Trypanosoma cruzi, which has three different parasite stages and a dixenous life cycle that includes colonization of the vertebrate and invertebrate hosts. During its life cycle, T. cruzi is subjected to stress conditions, including variations in nutrient availability and pH, which impact parasite survival and differentiation. The plasticity of mitochondrial function in trypanosomatids has been defined as mitochondrial activity related to substrate availability. Thus, mitochondrial remodeling and autophagy, which is a constitutive cellular process of turnover and recycling of cellular components, may constitute a response to the nutritional and pH stress in the host. To assess these processes, epimastigotes were subjected to acidic, alkaline, and nutritional stress conditions, and mitochondrial function and its influence on the autophagic process were evaluated. Our data demonstrated that the three stress conditions affected the mitochondrial structure, inducing organelle swelling and impaired oxidative phosphorylation. Stressed epimastigotes produced increased ROS levels and overexpressed antioxidant enzymes. The stress conditions resulted in an increase in the number of autophagosomes and exacerbated the expression of different autophagy-related genes (Atgs). A correlation between mitochondrial dysfunction and autophagic phenotypes was also observed. After 24 h, acid stress and nutritional deprivation induced metacyclogenesis phenotypes (mitochondrial remodeling and autophagy). On the other hand, alkaline stress was transient due to insect blood feeding and culminated in an increase in autophagic flux as a survival mechanism.
恰加斯病是一种在拉丁美洲流行的被忽视的疾病，主要影响农村人口。恰加斯病的病原体是原生动物克氏锥虫，它有三个不同的寄生虫阶段和一个两性生殖的生命周期，包括在脊椎动物和无脊椎动物宿主中的定殖。在其生命周期中，克氏锥虫受到应激条件的影响，包括营养物质可用性和 pH 值的变化，这些变化影响寄生虫的存活和分化。线粒体功能在锥虫中的可塑性被定义为与底物可用性相关的线粒体活性。因此，线粒体重塑和自噬，这是一个细胞成分的周转和再循环的组成性细胞过程，可能构成对宿主营养和 pH 应激的反应。为了评估这些过程，我们将滋养体置于酸性、碱性和营养应激条件下，并评估线粒体功能及其对自噬过程的影响。我们的数据表明，三种应激条件影响了线粒体结构，诱导细胞器肿胀和氧化磷酸化受损。应激滋养体产生增加的 ROS 水平和过表达抗氧化酶。应激条件导致自噬体数量增加，并加剧不同自噬相关基因（Atgs）的表达。还观察到线粒体功能障碍与自噬表型之间的相关性。在 24 小时后，酸应激和营养剥夺诱导了变形虫发生表型（线粒体重塑和自噬）。另一方面，碱性应激是短暂的，因为昆虫血液摄入，并最终导致自噬通量增加作为一种生存机制。
