Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells

• Published in: PloS one Vol. 17; no. 12; p. e0278516
• Main Authors: Hernandez, Arlet, Sonavane, Manoj, Smith, Kelly R, Seiger, Jensyn, Migaud, Marie E, Gassman, Natalie R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.12.2022; Public Library of Science (PLoS)
• Subjects: Apoptosis; Biology and Life Sciences; Carbohydrates; Cell cycle; Cell death; Chemical properties; Cigarettes; Cytotoxicity; Dihydroxyacetone - pharmacology; Dihydroxyacetone phosphate; Electronic cigarettes; Electronic Nicotine Delivery Systems; Glycolysis; Health risks; Hepatocytes; Liver; Liver cells; Medicine and Health Sciences; Melanoma; Metabolic pathways; Metabolism; Mitochondria; Monosaccharides; Nutrients; Oxidative phosphorylation; Oxygen; Phosphorylation; Physiological aspects; Reactive Oxygen Species; Signal transduction; Signaling; Smoking; Social Sciences; Stress (Physiology); Sugars; Tanning; TOR protein; Toxicity; Vaping; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0278516

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.