Skip to Main content Skip to Navigation

Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells

Abstract : Succinate dehydrogenase (SDH) inhibitors (SDHIs) are used worldwide to limit the proliferation of molds on plants and plant products. However, as SDH, also known as respiratory chain (RC) complex II, is a universal component of mitochondria from living organisms, highly conserved through evolution, the specificity of these inhibitors toward fungi warrants investigation. We first establish that the human, honeybee, earthworm and fungal SDHs are all sensitive to the eight SDHIs tested, albeit with varying IC50 values, generally in the micromolar range. In addition to SDH, we observed that five of the SDHIs, mostly from the latest generation, inhibit the activity of RC complex III. Finally, we show that the provision of glucose ad libitum in the cell culture medium, while simultaneously providing sufficient ATP and reducing power for antioxidant enzymes through glycolysis, allows the growth of RC-deficient cells, fully masking the deleterious effect of SDHIs. As a result, when glutamine is the major carbon source, the presence of SDHIs leads to time-dependent cell death. This process is significantly accelerated in fibroblasts derived from patients with neurological or neurodegenerative diseases due to RC impairment (encephalopathy originating from a partial SDH defect) and/or hypersensitivity to oxidative insults (Friedreich ataxia, familial Alzheimer's disease).
Complete list of metadatas

Cited literature [61 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02409310
Contributor : Myriam Bodescot <>
Submitted on : Friday, December 13, 2019 - 1:40:35 PM
Last modification on : Friday, March 27, 2020 - 2:50:19 AM

File

journal.pone.0224132.pdf
Publication funded by an institution

Identifiers

Citation

Paule Bénit, Agathe Kahn, Dominique Chretien, Sylvie Bortoli, Laurence Huc, et al.. Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells. PLoS ONE, Public Library of Science, 2019, 14 (11), pp.e0224132. ⟨10.1371/journal.pone.0224132⟩. ⟨inserm-02409310⟩

Share

Metrics

Record views

119

Files downloads

190