Starvation and pH stress conditions induced mitochondrial dysfunction, ROS production and autophagy in Trypanosoma cruzi epimastigotes

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Article

Pedra-Rezende, Yasmin¹  Fernandes, Michelle C.^1,2  Mesquita-Rodrigues, Camila^1,3  Stiebler, Renata¹  Bombaca, Ana Cristina S.¹  Pinho, Nathalia⁴  Cuervo, Patricia⁴  De Castro, Solange L.¹  Menna-Barreto, Rubem F. S.¹ 

[1] Fundacao Oswaldo Cruz, Lab Biol Celular, Inst Oswaldo Cruz, Rio De Janeiro, Brazil

[2] Fundacao Ctr Educ Distancia Cecierj Estado Rio de, Diretoria Extensao, Tres Rios, RJ, Brazil

[3] Univ Estado Rio de Janeiro, Inst Biol Roberto Alcantara Gomes, Lab Neurofisiol, Rio De Janeiro, Brazil

[4] Fundacao Oswaldo Cruz, Lab Pesquisa Leishmanioses, Inst Oswaldo Cruz, Rio De Janeiro, Brazil

关键词: Trypanosoma cruzi;    Mitochondria;    pH stress;    Nutritional deprivation;    Autophagy;   

DOI  :  10.1016/j.bbadis.2020.166028

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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