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

Author:

Qiu Kangqiang,Zou Weiwei,Fang Hongbao,Hao Mingang,Mehta KritikaORCID,Tian Zhiqi,Guan Jun-LinORCID,Zhang KaiORCID,Huang TaoshengORCID,Diao JiajieORCID

Abstract

AbstractMitochondria 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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