Phospholipids are the building blocks of biological membranes. Membranes leverage the amphipathic chemistry of lipids to form bilayers that encapsulate a cell and its multitude of organelles. Such compartmentalization has enabled cells to separate biochemical pathways, establish specialized functions that can respond when appropriate, and adapt to constantly fluctuating metabolic conditions. The Claypool laboratory’s research focus is on the underappreciated contribution of the mitochondrion to cellular phospholipid metabolism. In addition to being the sole producer of the canonical mitochondrial lipid, cardiolipin (CL), the mitochondrion hosts one of the two major pathways in a cell for the production of phosphatidylethanolamine (PE). Ablation of the mitochondrial capacity to synthesize either CL or PE is embryonically lethal in mice. The mitochondrial pathway of PE production therefore provides a pool of this lipid that cannot be replaced by the other three PE biosynthetic pathways. Moreover, in the yeast Saccharomyces cerevisiae the combined absence of CL and PE is synthetically lethal. Thus, both CL and PE are crucial for mammalian development and have distinct and yet overlapping properties that are essential not only for mitochondrial function, but life itself.

The research objectives of our current projects are:

1. To fill in the numerous structural and cell biological gaps in our understanding of the mitochondrial phosphatidylethanolamine biosynthetic pathway.
2. To Determine the physiological function(s) of TAZ-based CL remodeling.
3. To understand how CL can influence the structure/function of a membrane protein, the ADP/ATP carrier, at a molecular level.

The long term goal of our basic research is to understand lipid assembly and remodeling pathways in the mitochondrion and relate deficits in these processes to human disease.