Optogenetic control of lysosome function

Ilyinsky, N. S.; Bukhalovich, S. M.; Bagaeva, D. F.; Nesterov, S. V.; Alekseev, A. A.; Tsybrov, F. M.; Bogorodskiy, A. O.; Moiseeva, O. V.; Vlasova, A. D.; Kovalev, K. V.; Mikhailov, A. E.; Rogachev, A. V.; Bamberg, E.; Ivanovich, V.; Borshchevskiy, V. I.

doi:10.1101/2023.08.02.551716

bioRxiv · 10.1101/2023.08.02.551716

Optogenetic control of lysosome function

Ilyinsky, N. S.·Bukhalovich, S. M.·Bagaeva, D. F.·Nesterov, S. V.·Alekseev, A. A.·Tsybrov, F. M.·Bogorodskiy, A. O.·Moiseeva, O. V.·Vlasova, A. D.·Kovalev, K. V.·Mikhailov, A. E.·Rogachev, A. V.·Bamberg, E.·Ivanovich, V.·Borshchevskiy, V. I.

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Abstract

Lysosome protective, metabolic, signaling functions are highly dependent on their pH. A lack of tools of high spatial and temporal resolution for pH control is a bottleneck of lysosome related cell research. Light-driven inward proton pump NsXeR, targeted to the lysosomes of mammalian cells, produces lysosome alkalization simply by light. Complementary use of outward proton pumping Arch3 rhodopsins in lysosomes offers an approach to vary pH in a range from around 5 to 6.5 in both directions (de-acidification and acidification). Lyso-NsXeR optogenetics efficiency was demonstrated, in particular, by its ability to inhibit lysosome proteolytic enzymes. Thus, optogenetic monitoring and regulation of the lysosome function, through pH control over a wide range, could serve as an approach to studying fundamental cell processes, and rational drug design.

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Ilyinsky, N. S., Bukhalovich, S. M., Bagaeva, D. F., Nesterov, S. V., Alekseev, A. A., Tsybrov, F. M., Bogorodskiy, A. O., Moiseeva, O. V., Vlasova, A. D., Kovalev, K. V., Mikhailov, A. E., Rogachev, A. V., Bamberg, E., Ivanovich, V., Borshchevskiy, V. I.. 2023-08-04. Optogenetic control of lysosome function. https://doi.org/10.1101/2023.08.02.551716

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