Optogenetic Control of Endoplasmic Reticulum–Mitochondria Tethering

The organelle interface emerges as a dynamic platform for a variety of biological responses. However, their study has been limited by the lack of tools to manipulate their occurrence in live cells spatiotemporally. Here, we report the development of a genetically encoded light-inducible tethering (LIT) system allowing the induction of contacts between endoplasmic reticulum (ER) and mitochondria, taking advantage of a pair of light-dependent heterodimerization called an iLID system. We demonstrate that the iLID-based LIT approach enables control of ER–mitochondria tethering with high spatiotemporal precision in various cell types including primary neurons, which will facilitate the functional study of ER–mitochondrial contacts.