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


Autoři: Paule Bénit aff001;  Agathe Kahn aff001;  Dominique Chretien aff001;  Sylvie Bortoli aff002;  Laurence Huc aff003;  Manuel Schiff aff001;  Anne-Paule Gimenez-Roqueplo aff005;  Judith Favier aff006;  Pierre Gressens aff001;  Malgorzata Rak aff001;  Pierre Rustin aff001
Působiště autorů: Université de Paris, NeuroDiderot, INSERM, Paris, France aff001;  Université de Paris, INSERM, UMR-S 1124, Paris, France aff002;  INRA UMR 1331 ToxAlim (Research Center in Food Toxicology), Université de Toulouse ENVT, INP, UPS, 180 Chemin de Tournefeuille, France aff003;  Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Service de neurologie et maladies métaboliques, Paris, France aff004;  Université de Paris, PARCC, INSERM, Equipe Labellisée par la Ligue contre le Cancer, Paris, France aff005;  Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France aff006
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224132

Souhrn

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).

Klíčová slova:

Earthworms – Fibroblasts – Glucose – Honey bees – Mitochondria – Sequence alignment – Glutamine – Quinones


Zdroje

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