Cellular biology is focused on understanding the interactions at organelle contact sites, especially between mitochondria and the endoplasmic reticulum (ER). These sites are crucial for the exchange of essential biomolecules, but studying them presents challenges due to the lack of tools. A novel strategy called “OrthoID” has been developed to address this challenge by identifying proteins that mediate organelle interactions. Traditional methods relied on the streptavidin-biotin binding pair system, but OrthoID introduces a synthetic binding pair, cucurbit[7]uril-adamantane, to capture a more comprehensive range of protein interactions.
OrthoID leverages proximity labeling techniques and orthogonal binding pair systems to rapidly and accurately label proteins involved in ER-mitochondria contacts. By combining different binding pair systems, OrthoID can identify both known and novel proteins that facilitate organelle communications. Through meticulous experiments, researchers have pinpointed multiple protein sets undergoing changes during critical cellular processes such as mitophagy. The method has demonstrated its efficacy in identifying proteins involved in organelle communication and uncovering new protein candidates like LRC59 with previously unknown roles at contact sites.
Prof. Kimoon Kim from POSTECH highlights the flexibility and modularity of OrthoID as its greatest strengths, allowing for the study of various organelle contact sites and complex cellular communications. Prof. Kyeng Min Park from Daegu Catholic University School of Medicine emphasizes the versatility of OrthoID as a research tool to decode cellular communication and aid in understanding cellular health, disease mechanisms, and developing therapeutic strategies. The collaboration involved scientists from multiple institutions, including POSTECH, Daegu Catholic University School of Medicine, and Seoul National University, supported by the National Research Foundation of Korea and Institute for Basic Science.
OrthoID’s ability to identify mediator proteins involved in organelle communication opens new avenues for exploring cellular functions and disease mechanisms. By overcoming the limitations of traditional methods, OrthoID provides a more precise and comprehensive understanding of the proteins involved in ER-mitochondria contacts. The method’s adaptability allows for the study of various organelle contact sites and the exploration of complex cellular communications, potentially leading to significant discoveries with implications for cellular health and therapeutic development. Overall, OrthoID represents a valuable tool in unraveling the complexities of cellular function at the molecular level.
