1.
Modulating inter-mitochondrial contacts to increase membrane potential for mitigating blue light damage.
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Wang, Y
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Qui, K
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Zou, W
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Amom, P
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Ganjawala, TH
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Lee, E
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Tian, Z
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Xu, X
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Huang, T
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Tsai, NP
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Shi, D
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Kang, P
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Bai, H
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Zacharias, AL
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Zhang, K
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Diao, J
Abstract:
Mitochondrial membrane potential (MMP) is essential for mitochondrial functions, yet current methods for modulating MMP lack precise spatial and temporal control. Here, we present an optogenetic system that enables reversible formation of inter-mitochondrial contacts (mito-contacts) with high spatiotemporal precision. Blue light stimulation induces rapid formation of mito-contacts, which fully dissipate upon cessation of illumination. These light-induced mito-contacts can enhance MMP, leading to increased ATP production under stress conditions. Moreover, in human retinal cells and C. elegans, high MMP induced by mito-contacts alleviates the deleterious effects of prolonged blue light exposure, restoring energy metabolism and extending organismal lifespan. This optogenetic approach provides a powerful tool for modulating MMP and offers potential therapeutic applications for diseases linked to mitochondrial dysfunction.
2.
Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts.
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Qiu, K
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Zou, W
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Fang, H
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Hao, M
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Mehta, K
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Tian, Z
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Guan, JL
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Zhang, K
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Huang, T
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Diao, J
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.