MITODANGER

The One Health concept highlights the need for transversal and multiscale approaches recognizing the interconnection between humans, animals, plants and their shared environment. Mitochondria are organelles ubiquitously found in eukaryotes. Derived from endosymbiotic bacteria, they play a vital role in energy production as well as in many cellular processes. It is considered that all physicochemical, parasitic and microbial influences that surround eukaryotic life are translated into changes in mitochondrial structure and function. Mitochondria thus provide the missing link between cellular, organismal and environmental health. In this context, we are engaged in understanding how mitochondria contribute to the adaptive responses observed under stressful conditions. We recently developed an automated and miniaturized pipeline (MITOMATICS) exploiting mitochondrial morphology as a marker for monitoring cellular health or damage. MITOMATICS uses proprietary software to enable fast, high-throughput and cost-effective analysis of mitochondrial morphology in live cells. Specific mito-signatures are produced, some of which signal cell safety whereas others are early predictors of cell danger. We propose to apply this innovative high-content (HCS) screening technology to assess the mitotoxicity of pesticides (used alone or in combination) present locally in Occitanie, in West African countries and in Arizona. Mechanistic experiments will be performed to characterize the cellular effects of pesticide mixtures that will be found to display a synergistic behavior in HCS. Then, we will determine whether the identified pesticide cocktails function as ototoxic substances in vivo (in the zebrafish model, plus pilot experiments in mice), if they act synergistically with noise to trigger hearing loss (an emerging environmental threat) or modify the response of cells derived from patients with autism spectrum disorder (for which environmental pollutants represent a risk factor).