Unlocking the Secrets of Mitochondria: Rapid Imaging for Environmental Health Assessment

2023-06-27 18:22:00

Here is an image where mitochondria appear in pink: these are the lungs and “power stations” that allow the cells (in green, with their nuclei in blue) to breathe, live and ensure their functions.

In healthy cells on the left, the mitochondria are rather long and interconnected, like a road network seen from the sky; while in cells stressed and damaged on the right, their network is splintered into a constellation of solitary mitochondria, which produce less energy and will eventually rush cells into the path of suicide.

Thus, mitochondria are a good barometer of the health of our cells, the architecture of their networks even going so far as to vary in tissues from individuals. sick. Thanks to the’confocal imaging in real time, using in particular robots high-content imaging, we can reveal in less than a second the contours of a living cell, its nucleus and unique “organelles” (the elements of a cell that carry out specific functions, such as the mitochondria precisely ), in order to study the effects of different pollutants on cells and their health.

Rapid imaging of mitochondria as a “whistleblower” in environmental health

Contamination of air, water, food products, soil pollution, noise pollution: measuring the impact of environmental risks on the health of organisms and ecosystems is not an easy task.

The images generated by the imaging platforms are processed by computer to provide valuable information on the effect of the many pollutants that surround us.

This is a step forward in deciphering the “exposome”, a notion introduced by the British Christopher Paul Wild in 2005 and which is defined as the totality of the exposures to which an individual is subjected throughout his life (from conception to death).

Indeed, the outdoor pollution (air, water, soil) and interior (home, office, car) not only have negative effects on our health (with the onset of chronic diseases) and that of ecosystems (which show an unprecedented drop in biodiversity and agricultural yields), but also a socio-economic cost enormous.

One in six deaths would be attributable to it each year, i.e. three more time than AIDS, tuberculosis and malaria combined. We are also constantly evolving in a “chemosphere” (a mixture of substances) whose risks are very poorly known: epidemiologists and toxicologists have only been able to assess the toxicity of a minimal fraction of 350,000 chemicals recorded since the 1960s in major national and regional chemical inventories (for production and commercial use).

The health and ecological impact of these compounds, which risk jeopardizing the integrity of the earth system, remains poorly characterized when studied separately. What’s more, their potential “cocktail effects” (the effects resulting from exposure to several substances at the same time, which are sometimes more harmful than a “single” exposure) are almost never tested, due to a lack of technologies. to this.

How to translate the reality of these multiple exposures at the level of an organism’s cells?

A new generation of toxicological tests without animal testing

It is at this level that the mitochondria have their say. Fragmentation of mitochondria and of the mitochondrial network is indeed an early reflection of their loss of functionality and therefore a marker pen environmental hazard.

The principle of the method is to to paint (with vital dyes) mitochondria and other constituents of cells cultured in vitro. The latter are primary human cells, or lines, of various tissue origins (skin, lung, kidney, intestine for example) and which will be exposed to toxic substances found in our environment, for example pesticides or particles. fine. There is no need here to sacrifice an animal for each experiment.

Thanks to software, a battery of parameters is calculated from the confocal microscopy images: the size of the mitochondria, their circularity and their degree of connectivity are part of the hundred or so descriptors possibilities which make it possible to highlight the deleterious effect of toxic substances, alone or in combination (cocktail effect).

The objective is to link initiating molecular events, such as exposure to these chemical substances, with harmfulness or toxicity, at different biological scales at the level of cells, tissues, organs and even individuals. If the mitochondria connect the toxicities and alterations expressed at the microscopic scale (cells) and the adverse effects and pathologies observed at the tissue scale, the uncertainty concerns the extrapolation of the toxicological data obtained in vitro to the possible effects on organisms and ecosystems.

Ultimately, this system could also make it possible to identify ingredients capable of protecting or restoring the “mitochondriomes” (all mitochondria) of cells exposed to pollutants.

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