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
Reference56 articles.
1. Burté, F., Carelli, V., Chinnery, P. F. & Yu-Wai-Man, P. Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat. Rev. Neurol. 11, 11–24 (2015).
2. Alshaabi, H., Heininger, M. & Cunniff, B. Dynamic regulation of subcellular mitochondrial position for localized metabolite levels. J. Biochem. 167, 109–117 (2020).
3. Friedman, J. R. & Nunnari, J. Mitochondrial form and function. Nature 505, 335–343 (2014).
4. Sun, N., Youle, R. J. & Finkel, T. The mitochondrial basis of aging. Mol. Cell 61, 654–666 (2016).
5. Wong, Y. C., Kim, S., Peng, W. & Krainc, D. Regulation and function of mitochondria–lysosome membrane contact sites in cellular homeostasis. Trends Cell Biol. 29, 500–513 (2019).
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