Trypanosoma cruzi Epimastigotes Are Able to Manage Internal Cholesterol Levels under Nutritional Lipid Stress Conditions

PLoS One. 2015 Jun 11;10(6):e0128949. doi: 10.1371/journal.pone.0128949. eCollection 2015.

Abstract

Trypanosoma cruzi epimastigotes store high amounts of cholesterol and cholesteryl esters in reservosomes. These unique organelles are responsible for cellular digestion by providing substrates for homeostasis and parasite differentiation. Here we demonstrate that under nutritional lipid stress, epimastigotes preferentially mobilized reservosome lipid stocks, instead of lipid bodies, leading to the consumption of parasite cholesterol reservoirs and production of ergosterol. Starved epimastigotes acquired more LDL-NBD-cholesterol by endocytosis and distributed the exogenous cholesterol to their membranes faster than control parasites. Moreover, the parasites were able to manage internal cholesterol levels, alternating between consumption and accumulation. With normal lipid availability, parasites esterified cholesterol exhibiting an ACAT-like activity that was sensitive to Avasimibe in a dose-dependent manner. This result also implies that exogenous cholesterol has a role in lipid reservoirs in epimastigotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Chloro-7-nitrobenzofurazan / analogs & derivatives
  • 4-Chloro-7-nitrobenzofurazan / metabolism
  • Cholesterol / analogs & derivatives
  • Cholesterol / metabolism*
  • Endocytosis
  • Ergosterol / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Lipids / analysis
  • Microscopy, Electron, Transmission
  • Protozoan Proteins / metabolism
  • Sterol O-Acyltransferase / metabolism
  • Trypanosoma cruzi / growth & development
  • Trypanosoma cruzi / metabolism*

Substances

  • 7-nitrobenz-2-oxa-1,3-diazol-4-ylcholesterol
  • Lipids
  • Protozoan Proteins
  • Cholesterol
  • Sterol O-Acyltransferase
  • 4-Chloro-7-nitrobenzofurazan
  • Ergosterol

Grants and funding

This work was supported by the following sources of funding: grants E-26/102.850/2012 from Fundação Carlos Chagas Filho de Amparo à Pesquisa no Estado do Rio de Janeiro (FAPERJ) e 305599/2010-0 from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) to NCS, Grants E26/110.576/2010 from Fundação Carlos Chagas Filho de Amparo à Pesquisa no Estado do Rio de Janeiro (FAPERJ) to WDS and NCS, Fellowship E-26/101.023/2011 from Fundação Carlos Chagas Filho de Amparo à Pesquisa no Estado do Rio de Janeiro (FAPERJ) to MGP.