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

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Josefina Hernández, Matías Gabrielli, Joaquín Costa, Antonio D. Uttaro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9428f774488a4c9aabdfd53576781405
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9428f774488a4c9aabdfd53576781405
record_format	dspace
spelling	oai:doaj.org-article:9428f774488a4c9aabdfd535767814052021-12-02T17:39:19ZPhagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis10.1038/s41598-021-88737-z2045-2322https://doaj.org/article/9428f774488a4c9aabdfd535767814052021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88737-zhttps://doaj.org/toc/2045-2322Abstract 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.Josefina HernándezMatías GabrielliJoaquín CostaAntonio D. UttaroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Josefina Hernández Matías Gabrielli Joaquín Costa Antonio D. Uttaro Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis
description	Abstract 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.
format	article
author	Josefina Hernández Matías Gabrielli Joaquín Costa Antonio D. Uttaro
author_facet	Josefina Hernández Matías Gabrielli Joaquín Costa Antonio D. Uttaro
author_sort	Josefina Hernández
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 Portfolio
publishDate	2021
url	https://doaj.org/article/9428f774488a4c9aabdfd53576781405
work_keys_str_mv	AT josefinahernandez phagocyticandpinocyticuptakeofcholesterolintetrahymenathermophilaimpactdifferentlyongeneregulationforsterolhomeostasis AT matiasgabrielli phagocyticandpinocyticuptakeofcholesterolintetrahymenathermophilaimpactdifferentlyongeneregulationforsterolhomeostasis AT joaquincosta phagocyticandpinocyticuptakeofcholesterolintetrahymenathermophilaimpactdifferentlyongeneregulationforsterolhomeostasis AT antonioduttaro phagocyticandpinocyticuptakeofcholesterolintetrahymenathermophilaimpactdifferentlyongeneregulationforsterolhomeostasis
_version_	1718379836353806336

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

Ejemplares similares