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Rapid manipulation of mitochondrial morphology in a living cell with iCMM.

Cell reports methods (2022-04-28)
Takafumi Miyamoto, Hideki Uosaki, Yuhei Mizunoe, Song-Iee Han, Satoi Goto, Daisuke Yamanaka, Masato Masuda, Yosuke Yoneyama, Hideki Nakamura, Naoko Hattori, Yoshinori Takeuchi, Hiroshi Ohno, Motohiro Sekiya, Takashi Matsuzaka, Fumihiko Hakuno, Shin-Ichiro Takahashi, Naoya Yahagi, Koichi Ito, Hitoshi Shimano
RÉSUMÉ

Engineered synthetic biomolecular devices that integrate elaborate information processing and precisely regulate living cell behavior have potential in various applications. Although devices that directly regulate key biomolecules constituting inherent biological systems exist, no devices have been developed to control intracellular membrane architecture, contributing to the spatiotemporal functions of these biomolecules. This study developed a synthetic biomolecular device, termed inducible counter mitochondrial morphology (iCMM), to manipulate mitochondrial morphology, an emerging informative property for understanding physiopathological cellular behaviors, on a minute timescale by using a chemically inducible dimerization system. Using iCMM, we determined cellular changes by altering mitochondrial morphology in an unprecedented manner. This approach serves as a platform for developing more sophisticated synthetic biomolecular devices to regulate biological systems by extending manipulation targets from conventional biomolecules to mitochondria. Furthermore, iCMM might serve as a tool for uncovering the biological significance of mitochondrial morphology in various physiopathological cellular processes.

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mTOR Inhibitor XI, Torin1, mTOR Inhibitor XI, Torin1, CAS 1222998-36-8, is a cell-permeable, highly potent, ATP-competitive inhibitor of mTOR and DNA-PK (IC50 = 4.32 and 6.34 nM, respectively).