Subcellular-Level Mitochondrial Energy Metabolism Response in the Fat Body of the German Cockroach Fed Abamectin

SIMPLE SUMMARY: To date, it is rare to study the effects of environmental toxicants (e.g., abamectin, a widely used pesticide) on mitochondrial energy metabolism in vitro from a subcellular level in insects, especially from an omics perspective (e.g., metabolomics) due to insufficient samples of mitochondria. The fat body of the German cockroach (Blattella germanica) plays an important role for detoxification, with responses of critical subcellular components (e.g., mitochondria) to abamectin. When B. germanica were fed abamectin, their in vitro mitochondrial morphology was affected, with changes in activity of key enzymes involved in energy metabolism. Furthermore, metabonomic analysis of in vitro mitochondria of B. germanica uncovered a set of metabolites and their pathways related to mitochondrial energy metabolism in response to abamectin feeding/stress. These molecules and pathways were primarily involved in ATP production and energy consumption including oxidative phosphorylation, TCA cycle, and pentose phosphate pathway. The current work is a good example of investigations on subcellular toxicology from multiple perspectives (morphology, physiology, and metabolomics). ABSTRACT: Mitochondria are the leading organelle for energy metabolism. The toxic effects of environmental toxicants on mitochondrial morphology, energy metabolism, and their determination of cell fate have already been broadly studied. However, minimal research exists on effects of environmental toxicants such as pesticides on mitochondrial energy metabolism at in vitro subcellular level, particularly from an omics perspectives (e.g., metabolomics). Here, German cockroach (Blattella germanica) was fed diets with (0.01 and 0.001 mg/mL) and without abamectin, and highly purified fat body mitochondria were isolated. Swelling measurement confirmed abnormal mitochondrial swelling caused by abamectin stress. The activity of two key mitochondrial energy metabolism-related enzymes, namely succinic dehydrogenase and isocitrate dehydrogenase, was significantly affected. The metabolomic responses of the isolated mitochondria to abamectin were analyzed via untargeted liquid chromatography/mass spectrometry metabolomics technology. Fifty-two differential metabolites (DMs) were identified in the mitochondria between the 0.001 mg/mL abamectin-fed and the control groups. Many of these DMs were significantly enriched in pathways involved in ATP production and energy consumption (e.g., oxidative phosphorylation, TCA cycle, and pentose phosphate pathway). Nineteen of the DMs were typically related to energy metabolism. This study is valuable for further understanding mitochondrial toxicology under environmental toxicants, particularly its subcellular level.