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

Kangqiang Qiu, Weiwei Zou, Hongbao Fang, Mingang Hao, Kritika Mehta, Zhiqi Tian, Jun-Lin Guan (), Kai Zhang (), Taosheng Huang () and Jiajie Diao ()
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Kangqiang Qiu: University of Cincinnati College of Medicine
Weiwei Zou: Cincinnati Children’s Hospital Medical Center
Hongbao Fang: University of Cincinnati College of Medicine
Mingang Hao: University of Cincinnati College of Medicine
Kritika Mehta: University of Illinois at Urbana-Champaign
Zhiqi Tian: University of Cincinnati College of Medicine
Jun-Lin Guan: University of Cincinnati College of Medicine
Kai Zhang: University of Illinois at Urbana-Champaign
Taosheng Huang: Cincinnati Children’s Hospital Medical Center
Jiajie Diao: University of Cincinnati College of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31970-5

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