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

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dc.creatorHernández, Josefina
dc.creatorGabrielli, Matías
dc.creatorCosta, Joaquín
dc.creatorUttaro, Antonio Domingo
dc.date.accessioned2022-04-04T16:13:58Z
dc.date.available2022-04-04T16:13:58Z
dc.date.issued2021-04-27
dc.descriptionThe 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 lineageses
dc.description.filFil: Herández, Josefina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (CONICET). Argentina.
dc.description.filFil: Gabrielli, Matías. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (CONICET). Argentina.
dc.description.filFil: Costa, Joaquín. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (CONICET). Argentina.
dc.description.filFil: Uttaro, Antonio Domingo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (CONICET). Argentina.
dc.description.sponsorshipFondo para la Investigación Científica y Tecnológica (FONCYT): Grant PICT 2016, N° 0933
dc.formatapplication/pdf
dc.format.extent1-11
dc.identifier.urihttp://hdl.handle.net/2133/23320
dc.language.isoenges
dc.publisherNature Researches
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-021-88737-zes
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-021-88737-z
dc.rightsopenAccesses
dc.rights.holderHernández, Josefinaes
dc.rights.holderGabrielli, Matíases
dc.rights.holderCosta, Joaquínes
dc.rights.holderUttaro, Antonio Domingoes
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectBiological Transportes
dc.subjectCholesteroles
dc.subjectGene Expression Regulationes
dc.subjectHomeostasises
dc.subjectTetrahymena Thermophilaes
dc.subjectEndoplasmic Reticulumes
dc.subjectSterolses
dc.titlePhagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasises
dc.typepublishedVersion
dc.typearticle
dc.typeartículo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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