Modulation of phospholipid metabolism by annexins
Lead Research Organisation:
University College London
Department Name: Institute of Ophthalmology
Abstract
Phospholipids are essential components of the human diet yet their excessive consumption, particularly in western societies is associated with obesity, diabetes and cardiovascular disease. Phospholipids are essential because they form the membranes that not only encapsulate all cells, they also form the membranes inside cells that partition cellular constituents into organelles. There are many different types of phospholipid, and these can serve both structural and signaling functions. We have observed abnormalities in a mutant mouse strain that lacks annexin 6, one of a large and abundant family of proteins that binds to phospholipids, that is strongly suggestive of defective phospholipid metabolism. The proposed research will use cells from these mice to investigate the expression and movement of certain phospholipids within these cells, and to understand how annexin 6 is involved in these activities.
Technical Summary
Annexin 6 is an abundant protein that binds to negatively-charged phospholipids in the presence of calcium. In mice lacking annexin 6 generated in our lab, we have observed a number of phenotype including the presence of microparticles in the blood, reduced phosphatidylserine in mitochondrial membranes, failure to deposit adipose tissue, that all suggest defective phospholipid metabolism and trafficking. Here, we will use adipocytes and hepatocytes from control and null mutant mice to investigate lipid trafficking and metabolism. Our approach will employ lipid purification and mass spec analysis, biochemistry, live cell imaging and analysis of mitochondrial function. This is a comprehensive programme of work that will provide new insight into annexin function, and in particular the role of annexin 6 in the regulation of phospholipid metabolism.
| Description | We elucidated the function of Anxa6 in this study. This is a protein we discovered many years ago which is involved in a number of cellular processes, but which has proven remarkably difficult to understand. Our research showed the AnxA6 is a critical regulator of mitochondria, the organelles within cells that are responsible for the generation of energy. In the absence of AnxA6 we observed that mitochondria fragment and become less efficient, and we showed that this is due to the loss of an interaction between AnxA6 and another mitochondrial protein named Drp1. The findings have important implication for understanding diseases in which AnxA6 protein levels may change, such as cancer and cardiovascular disease. |
| Exploitation Route | The development of small molecule activators or stabilisers of AnxA6 could be useful in helping to preserve mitochondrial function in disease. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Joint study on annexin A6 function |
| Organisation | University of Münster |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Collaborative work with Professor Volker Gerke of the University of Muenster. |
| Start Year | 1994 |