Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis

The ciliate Tetrahymena thermophila can either synthesize tetrahymanol or when available, assimilate and modify sterols from its diet. This metabolic shift is mainly driven by transcriptional regulation of genes for tetrahymanol synthesis (TS) and sterol bioconversion (SB). The mechanistic details o...

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Detalles Bibliográficos
Autores principales: Hernández, Josefina, Gabrielli, Matías, Costa, Joaquín, Uttaro, Antonio Domingo
Lenguaje:Inglés
Publicado: Nature Research 2022
Materias:
Biological Transport
Cholesterol
Gene Expression Regulation
Homeostasis
Tetrahymena Thermophila
Endoplasmic Reticulum
Sterols
Acceso en línea:http://hdl.handle.net/2133/23320
http://hdl.handle.net/2133/23320
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-23320
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Biological Transport
Cholesterol
Gene Expression Regulation
Homeostasis
Tetrahymena Thermophila
Endoplasmic Reticulum
Sterols
spellingShingle Biological Transport
Cholesterol
Gene Expression Regulation
Homeostasis
Tetrahymena Thermophila
Endoplasmic Reticulum
Sterols
Hernández, Josefina
Gabrielli, Matías
Costa, Joaquín
Uttaro, Antonio Domingo
Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
topic_facet Biological Transport
Cholesterol
Gene Expression Regulation
Homeostasis
Tetrahymena Thermophila
Endoplasmic Reticulum
Sterols
description The ciliate Tetrahymena thermophila can either synthesize tetrahymanol or when available, assimilate and modify sterols from its diet. This metabolic shift is mainly driven by transcriptional regulation of genes for tetrahymanol synthesis (TS) and sterol bioconversion (SB). The mechanistic details of sterol uptake, intracellular trafficking and the associated gene expression changes are unknown. By following cholesterol incorporation over time in a conditional phagocytosis-deficient mutant, we found that although phagocytosis is the main sterol intake route, a secondary endocytic pathway exists. Different expression patterns for TS and SB genes were associated with these entry mechanisms. Squalene synthase was down-regulated by a massive cholesterol intake only attainable by phagocytosis-proficient cells, whereas C22-sterol desaturase required ten times less cholesterol and was up-regulated in both wild-type and mutant cells. These patterns are suggestive of at least two different signaling pathways. Sterol trafficking beyond phagosomes and esterification was impaired by the NPC1 inhibitor U18666A. NPC1 is a protein that mediates cholesterol export from late endosomes/lysosomes in mammalian cells. U18666A also produced a delay in the transcriptional response to cholesterol, suggesting that the regulatory signals are triggered between lysosomes and the endoplasmic reticulum. These findings could hint at partial conservation of sterol homeostasis between eukaryote lineages
author Hernández, Josefina
Gabrielli, Matías
Costa, Joaquín
Uttaro, Antonio Domingo
author_facet Hernández, Josefina
Gabrielli, Matías
Costa, Joaquín
Uttaro, Antonio Domingo
author_sort Hernández, Josefina
title Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
title_short Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
title_full Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
title_fullStr Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
title_full_unstemmed Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
title_sort phagocytic and pinocytic uptake of cholesterol in tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
publisher Nature Research
publishDate 2022
url http://hdl.handle.net/2133/23320
http://hdl.handle.net/2133/23320
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bdutipo_str Repositorios
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