2,4,6-trinitrotoluene causes mitochondrial toxicity in Caenorhabditis elegans by affecting electron transport

• Published in: Environmental research 2024-07, Vol.252, p.118820-118820, Article 118820
• Main Authors: Zhou, Yanping, Wang, Chunyan, Nie, Yaguang, Wu, Lijun, Xu, An
• Format: Article
• Language: English
• Subjects: acute exposure; adenosine triphosphate; antioxidant activity; C. elegans; Caenorhabditis elegans; electron transfer; fluorescence; genes; genetically modified organisms; homeodomain proteins; homeostasis; membrane potential; mitochondria; mitochondrial membrane; Mitochondrial toxicity; mt UPR; pollution; superoxide dismutase; TNT; toxicity; transcription factors; trinitrotoluene; unfolded protein response
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2024.118820

As a typical energetic compound widely used in military activities, 2,4,6-trinitrotoluene (TNT) has attracted great attention in recent years due to its heavy pollution and wide distribution in and around the training facilities, firing ranges, and demolition sites. However, the subcellular targets and the underlying toxic mechanism of TNT remain largely unknown. In this study, we explored the toxic effects of TNT biological reduction on the mitochondrial function and homeostasis in Caenorhabditis elegans (C. elegans). With short-term exposure of L4 larvae, 10–1000 ng/mL TNT reduced mitochondrial membrane potential and adenosine triphosphate (ATP) content, which was associated with decreased expression of specific mitochondrial complex involving gas-1 and mev-1 genes. Using fluorescence-labeled transgenic nematodes, we found that fluorescence expression of sod-3 (muls84) and gst-4 (dvls19) was increased, suggesting that TNT disrupted the mitochondrial antioxidant defense system. Furthermore, 10 ng/mL TNT exposure increased the expression of the autophagy-related gene pink-1 and activated mitochondrial unfolded protein response (mt UPR), which was indicated by the increased expression of mitochondrial stress activated transcription factor atfs-1, ubiquitin-like protein ubl-5, and homeobox protein dve-1. Our findings demonstrated that TNT biological reduction caused mitochondrial dysfunction and the development of mt UPR protective stress responses, and provided a basis for determining the potential risks of energetic compounds to living organisms. [Display omitted] •10–1000 ng/mL TNT reduced mitochondrial membrane potential and ATP in C. elegans.•TNT caused imbalance of metabolism by reducing the expression of complex I-III.•ETC and ROS abnormity resulted in antioxidation as revealed by sod-3 and gst-4.•Autophagy and mt UPR were activated to mitigate TNT induced mitochondrial toxicity.