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.

南美锥虫病是拉丁美洲被忽视的一种地方病，主要影响农村人口。恰加斯病的病原体是原生动物锥虫锥虫，它具有三个不同的寄生虫阶段和一个包括脊椎动物和无脊椎动物宿主定殖的双生命周期。T. cruzi在其生命周期中会受到压力条件的影响，包括营养物利用率和pH的变化，这会影响寄生虫的生存和分化。锥虫中线粒体功能的可塑性已被定义为与底物可用性相关的线粒体活性。因此，线粒体重塑和自噬是细胞成分更新和循环的组成性细胞过程，可能构成对宿主营养和pH胁迫的反应。为了评估这些过程，将淫前鞭毛纲动物置于酸性，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，三种胁迫条件影响线粒体结构，诱导细胞器肿胀和氧化磷酸化受损。应激的鞭毛鞭毛虫产生的ROS水平升高，抗氧化酶过度表达。应激条件导致自噬体数量增加，并加剧了不同自噬相关基因（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。24小时后，酸胁迫和营养剥夺诱导了metacyclogenesis表型（线粒体重塑和自噬）。另一方面，由于昆虫的血液喂养，碱性应激是短暂的，最终导致自噬通量的增加作为生存机制。还观察到线粒体功能障碍与自噬表型之间的相关性。24小时后，酸胁迫和营养剥夺诱导了metacyclogenesis表型（线粒体重塑和自噬）。另一方面，由于昆虫的血液喂养，碱性应激是短暂的，最终导致自噬通量的增加作为生存机制。还观察到线粒体功能障碍与自噬表型之间的相关性。24小时后，酸胁迫和营养剥夺诱导了metacyclogenesis表型（线粒体重塑和自噬）。另一方面，由于昆虫的血液喂养，碱性应激是短暂的，最终导致自噬通量的增加作为生存机制。