Tracking spatiotemporal distribution of organelle contacts in vivo with SPLICS reporters.

Organelle contact sites are crucial for cellular function, enabling the exchange of lipids, ions, and other molecules between different organelles. The ability to track these contact sites in vivo has been significantly advanced by the development of SPLICS (Split-GFP-based Contact Site Sensors) reporters, which have provided unprecedented insights into the intricate network of organelle communication. This innovative and powerful tool allows the real-time visualization of different organelle interactions in living cells and in vivo thus unraveling the complexity of their dynamic in the context of cellular homeostasis. Recent studies highlighted the dynamic nature of organelle contact sites either in terms of tethering/untethering and of movement of the contact itself in time and space: whether unique temporal behaviors and contact site-specific dynamics of different organelle interactions exist is currently unknown. In this study, we investigated the spatiotemporal distribution of various organelle contact sites using time-lapse in vitro and in vivo imaging and discovered an evolutionarily conserved dynamic pattern among different contact sites, influenced by the specific partner organelles involved. These findings highlight the importance of spatial and temporal regulation at organelle contact sites, which may underlie their diverse physiological functions. The discovery of contact site-specific dynamics opens new avenues for understanding the regulation of organelle interactions in health and disease, with potential implications for developing targeted therapeutic strategies.