Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells.
Dihydroxyacetone (DHA) is the active ingredient in sunless tanning products and a combustion product from e-juices in electronic cigarettes (e-cigarettes). DHA is rapidly absorbed in cells and tissues and incorporated into several metabolic pathways through its conversion to dihydroxyacetone phospha...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0278516 |
| _version_ | 1797954001071767552 |
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| author | Arlet Hernandez Manoj Sonavane Kelly R Smith Jensyn Seiger Marie E Migaud Natalie R Gassman |
| author_facet | Arlet Hernandez Manoj Sonavane Kelly R Smith Jensyn Seiger Marie E Migaud Natalie R Gassman |
| author_sort | Arlet Hernandez |
| collection | DOAJ |
| description | Dihydroxyacetone (DHA) is the active ingredient in sunless tanning products and a combustion product from e-juices in electronic cigarettes (e-cigarettes). DHA is rapidly absorbed in cells and tissues and incorporated into several metabolic pathways through its conversion to dihydroxyacetone phosphate (DHAP). Previous studies have shown DHA induces cell cycle arrest, reactive oxygen species, and mitochondrial dysfunction, though the extent of these effects is highly cell-type specific. Here, we investigate DHA exposure effects in the metabolically active, HepG3 (C3A) cell line. Metabolic and mitochondrial changes were evaluated by characterizing the effects of DHA in metabolic pathways and nutrient-sensing mechanisms through mTOR-specific signaling. We also examined cytotoxicity and investigated the cell death mechanism induced by DHA exposure in HepG3 cells. Millimolar doses of DHA were cytotoxic and suppressed glycolysis and oxidative phosphorylation pathways. Nutrient sensing through mTOR was altered at both short and long time points. Increased mitochondrial reactive oxygen species (ROS) and mitochondrial-specific injury induced cell cycle arrest and cell death through a non-classical apoptotic mechanism. Despite its carbohydrate nature, millimolar doses of DHA are toxic to liver cells and may pose a significant health risk when higher concentrations are absorbed through e-cigarettes or spray tanning. |
| first_indexed | 2024-04-10T23:10:51Z |
| format | Article |
| id | doaj.art-1f16a9ed5da14c8184aa2a8a83b1dbc3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T23:10:51Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1f16a9ed5da14c8184aa2a8a83b1dbc32023-01-13T05:31:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011712e027851610.1371/journal.pone.0278516Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells.Arlet HernandezManoj SonavaneKelly R SmithJensyn SeigerMarie E MigaudNatalie R GassmanDihydroxyacetone (DHA) is the active ingredient in sunless tanning products and a combustion product from e-juices in electronic cigarettes (e-cigarettes). DHA is rapidly absorbed in cells and tissues and incorporated into several metabolic pathways through its conversion to dihydroxyacetone phosphate (DHAP). Previous studies have shown DHA induces cell cycle arrest, reactive oxygen species, and mitochondrial dysfunction, though the extent of these effects is highly cell-type specific. Here, we investigate DHA exposure effects in the metabolically active, HepG3 (C3A) cell line. Metabolic and mitochondrial changes were evaluated by characterizing the effects of DHA in metabolic pathways and nutrient-sensing mechanisms through mTOR-specific signaling. We also examined cytotoxicity and investigated the cell death mechanism induced by DHA exposure in HepG3 cells. Millimolar doses of DHA were cytotoxic and suppressed glycolysis and oxidative phosphorylation pathways. Nutrient sensing through mTOR was altered at both short and long time points. Increased mitochondrial reactive oxygen species (ROS) and mitochondrial-specific injury induced cell cycle arrest and cell death through a non-classical apoptotic mechanism. Despite its carbohydrate nature, millimolar doses of DHA are toxic to liver cells and may pose a significant health risk when higher concentrations are absorbed through e-cigarettes or spray tanning.https://doi.org/10.1371/journal.pone.0278516 |
| spellingShingle | Arlet Hernandez Manoj Sonavane Kelly R Smith Jensyn Seiger Marie E Migaud Natalie R Gassman Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells. PLoS ONE |
| title | Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells. |
| title_full | Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells. |
| title_fullStr | Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells. |
| title_full_unstemmed | Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells. |
| title_short | Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells. |
| title_sort | dihydroxyacetone suppresses mtor nutrient signaling and induces mitochondrial stress in liver cells |
| url | https://doi.org/10.1371/journal.pone.0278516 |
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