4.8 Article

Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts

Journal

NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31970-5

Keywords

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Funding

  1. National Institutes of Health (NIH) [R35GM128837, R21AG061600, R01GM132438, R01MH124827]

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Researchers have developed a method to induce mitochondrial fission with spatiotemporal accuracy by optogenetically controlling mitochondria-lysosome contacts (MLCs). The optogenetic MLCs system provides a platform for studying mitochondrial fission and treating mitochondrial diseases.
Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria-lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers. Real-time optogenetic induction of mitochondrial fission is tracked in living cells to measure the fission rate. The optogenetic method partially restores the mitochondrial functions of SLC25A46(-/-) cells, which display defects in mitochondrial fission and hyperfused mitochondria. The optogenetic MLCs system thus provides a platform for studying mitochondrial fission and treating mitochondrial diseases.

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