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

Qiu, Kangqiang; Zou, Weiwei; Fang, Hongbao; Hao, Mingang; Mehta, Kritika; Tian, Zhiqi; Guan, Jun-Lin; Zhang, Kai et al. · Nat Commun · 2022

basic_science · Level V

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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<sup>-/-</sup> 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.

Medical subject headings