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, Jiajie Diao
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.