Researchers at Duke-NUS Medical School and colleagues in Singapore have identified a protein that transports degraded membrane lipids from lysosomes, cellular organelles that are the cell’s breaking factories. The results are published in Proceedings of the National Academy of SciencesAnd the Increased understanding of the particle’s role in health and disease.
“Particles are found in cells throughout the human body, and they are small organelles responsible for breaking down cellular waste products and salvaging reusable molecules as building blocks for cellular components,” explained Ms. With a PhD track in Biology and Integrated Medicine at Duke-NUS. “When lysosomes are disrupted by rare genetic disorders, it leads to the accumulation of toxic cellular wastes and affects other organelles, causing cellular and organic diseases such as neurodegeneration.”
In the study, Ms He and a multidisciplinary team of scientists in Singapore examined a panel of transporter proteins whose functions have not been fully elucidated. The proteins they examined belong to a group called the major facilitator family (MFS), which is important for transporting molecules across cell membranes.
Their findings revealed that an MFS protein called Spns1 transports the hydrolyzed products of two phospholipids, phosphatidylcholine and phosphatidylethanolamine-; They are important building blocks for the structure and function of living cells-; Outside the lysosomes into the cytoplasm. The two molecules then pass through pathways that recycle them into their original lipid forms so they can be re-integrated into the cell.
“Scientists know a lot about the molecular processes involved in breaking down and transporting certain molecules out of lysosomes,” added Dr. Alvin Cook, who is also the study’s first co-author and a postdoctoral research fellow in Cardiovascular and Metabolic Disorders. (CVMD) program at Duke-NUS. “But when it comes to the two lipids, phosphatidylcholine and phosphatidylethanolamine which are the most abundant phospholipids in cell membranes, very little is known.”
The scientists further found that Spns1 deficiency in cells and preclinical models led to the pathological accumulation of lipolytic metabolites within lysosomes. This buildup has led to various disease states, including signs of increased inflammation.
Historically, identification of lysosomal lipid transporters has been difficult, which has limited our understanding of the role of lysosomes in lipid metabolism and disease. This study provides a framework for investigating how this novel vector functions and its role in health and disease.”
Professor David Silver, co-first author of the study and deputy director of the CVMD Program at Duke-NUS
“This has been a wonderful collaboration,” said Associate Professor Federico Torta, one of the study’s senior authors from the Yong Lo Lin School of Medicine at the National University of Singapore. “We helped elucidate the function of Spns1 by integrating the results of our colleagues at Duke-NUS with our lipid data. Isolated mass spectrometry-based lipids of tissues, cells and lysosomes allowed quantitative and qualitative changes in their lipid composition to be determined with high accuracy and sensitivity.”
he, m, et al. (2022) Spns1 is a lysophospholipid transporter that mediates the rescue of phosphorylated lysosomes. PNAS. doi.org/10.1073/pnas.2210353119.