as lipids and calcium ions, which are vital for cellular function and homeostasis. The identification of key proteins involved in organelle communication is crucial for understanding the underlying mechanisms of various cellular processes and diseases.
Recently, a collaboration of researchers has developed a new strategy for identifying these key proteins in organelle communication. This innovative approach enhances our capability to pinpoint proteins that are crucial for organelle interactions within specific spatial and temporal contexts.
to address the difficulties in studying ER-mitochondria contact sites. The communication between these organelles is essential for the maintenance of cellular homeostasis, involving lipids and calcium. Disruptions in this communication have been linked to the development of various diseases, including neurodegenerative disorders. Understanding the mechanisms governing organelle interactions is crucial, but it presents challenges due to the lack of available tools. In response to this need, scientists from POSTECH have developed a new approach called “OrthoID” to tackle the complexities of studying these dynamic complexes.The Daegu Catholic University School of Medicine and Seoul National University collaborated on a project featured in Nature Communications, aiming to improve the identification of proteins involved in crucial cellular interactions. The traditional method of using the streptavidin-biotin (SA-BT) binding pair system has limitations in capturing the full range of protein interactions between organelles. To address this, OrthoID introduces a synthetic bind to enhance the accuracy of identifying these mediator proteins.The researchers used a combination of binding pair systems, including cucurbit[7]uril-adamantane (CB[7]-Ad), to complement SA-BT. This pairing allowed for a more precise identification and analysis of mediator proteins that move between the ER and mitochondria, leading to a deeper understanding of the proteins involved in organelle contact sites and their roles in cellular functions and disease mechanisms.
Through careful experiments, the researchers showed that OrthoID is effective in quickly and accurately labeling proteins involved in the dynamic processes of organelle communication. Using proactive measures, they demonstrated the efficacy of OrthoID in rapidly and accurately labeling proteins involved in the dynamic processes of organelle communication. Overall, this allowed for a more thorough exploration of proteins involved in organelle communication and the roles they play in cellular functions and disease mechanisms.proximity labeling techniques, such as APEX2 and TurboID, use orthogonal binding pair systems to label and isolate proteins involved in the interactions between mitochondria and the ER. This method not only identifies known proteins in these interactions but also reveals new protein candidates, like LRC59, whose roles at the contact site were previously unknown. Additionally, the researchers were able to pinpoint multiple sets of proteins undergoing structural and locational changes at the ER-mitochondria junction during important cellular processes, such as mitophagy, which targets damaged mitochondria for destruction.degradation.
According to Prof. Kimoon Kim, who led the research from POSTECH, one of the greatest strengths of OrthoID is its flexibility and modularity. This adaptability allows for studying various organelle contact sites and also opens up new possibilities for exploring complex cellular communications, overcoming the technical limitations of existing methods.”
Prof. Kyeng Min Park from Daegu Catholic University School of Medicine also commented, “OrthoID is a versatile and valuable research tool designed to decipher the complex language of cellular communication. It is expected to enable discoveries that will have significant implications.”The researchers’ goal was to promote cellular health, uncover the causes of diseases, and encourage the creation of new treatments. The team, which consisted of Prof. Kimoon Kim, Dr. Ara Lee, Dr. Gihyun Sung, Prof. Kyeng Min Park, Prof. Hyun-Woo Rhee, and Prof. Jong-Seo Kim, collaborated across various departments and universities. Their work received support from the National Research Foundation.The study was conducted by researchers from the National Research Foundation of Korea (NRF) and the Institute for Basic Science (IBS).