Document Type

Article

Publication Date

2021

Abstract

Exposure to xenobiotic compounds, such as pesticides, is an emerging risk factor for Type II diabetes mellitus (T2DM). However, whether metabolic disturbances are induced specifically by xenobiotic compounds and the potential link to T2DM are presently unknown. To investigate these potential disturbances in response to xenobiotic stress, the tricarboxylic acid (TCA) cycle was analyzed given its central role in mitochondrial metabolism. To control for environmental confounds potentially affecting metabolism, we proposed the two-spotted spider mite (Tetranychus urticae) as a novel model organism to study xenobiotic specific metabolic disturbances. Due to the mite’s ability to rapidly develop pesticide resistance, comparisons between pesticide-adapted and pesticide-non-adapted mites allowed observations of metabolic changes solely due to pesticide stress. Mite orthologs for the human TCA cycle enzymes were first found through sequence alignment searches. Subsequently, spider mite transcriptomic and metabolomic data were extracted from prior studies investigating mite responses to plant xenobiotic compounds. When compared to pesticide-adapted mites, the pesticide-non-adapted mites exhibited decreased expression of five genes: FH, MDH1, MDH2, IDH3A, and CS, likely resulting in the suppression of the TCA cycle upon xenobiotic exposure. These results suggest that certain genes within the TCA cycle may be selectively sensitive to xenobiotic compounds. In summary, we have identified potential target genes and enzymes to further investigate how xenobiotic compounds disturb metabolism.

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