25 May 2022

Mitochondrial Activators

Light-activated mitochondria extended the life of experimental worms

Sergey Vasiliev, Naked Science

Scientists have created an artificial protein — a proton pump that supports the electrical potential on the membranes of mitochondria. The mtON system is activated by light, automatically enhancing the potential and production of ATP molecules. Working in the mitochondria of nematodes, she increased their life expectancy in some cases by a third. Biologists write about this in an article that has not yet passed an authoritative review and is still available in the bioRxiv preprint library (Berry et al., Optogenetic rejuvenation of mitochondrial membrane potential extends C.elegans lifespan).

Mitochondria are small and numerous organelles of eukaryotes. They play the role of "power plants", supplying intracellular processes with energy in the form of ATP molecules, and the body as a whole with additional heat. The condition and functionality of mitochondria degrades markedly with age. Among other things, the electrical potential on their internal membranes decreases, thanks to which ATP synthesis occurs. Therefore, aging researchers pay special attention to mitochondria.

The work of mitochondria is also being studied by a team of biologists from Germany and the USA, led by Andrew Wojtovich from the University of Washington Medical Center. Back in 2020, they received an artificial protein — a proton pump that pumps charges through the mitochondrial membranes, creating an electrical potential. The synthetic mtON pump, created on the basis of a protein from fungal cells, is able to react to light, working more actively and increasing the transmembrane potential. At the same time, scientists demonstrated the work of mtON introduced into the cells of Caenorhabditis elegans worms.

In the new work, Wojtowicz and colleagues studied how the work of mtON affects the lifespan of nematodes. To do this, they received new C lines. elegans, to which modified proton pumps were injected either by DNA injection or by the CRISPR/Cas9 method. The work of the new protein was started in the presence of a cofactor — retinal. The lifespan of such worms turned out to be longer than that of the same animals that did not receive retinal for mtON activation. The life extension ranged from six to 38 percent, depending on the intensity of lighting and the nematode line used.

According to the authors of the work, these results show that maintaining the mitochondrial membrane potential has a noticeable positive effect on longevity. Now scientists plan to test the mtON system on more complex animals, including fruit flies and mice. Perhaps in the future, injections of such light-activated proteins will form the basis of new drugs that slow down aging.

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