Steven Claypool

Phospholipids are the building blocks of biological membranes which enable cells to separate biochemical pathways, establish specialized functions that can respond when appropriate, and adapt to constantly fluctuating metabolic conditions. My 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. Moreover, in the yeast Saccharomyces cerevisiae, the combined absence of CL and PE is synthetically lethal. Using a combination of yeast and mammalian cell culture models, my lab currently has three major ongoing projects centered on different aspects of mitochondrial phospholipid metabolism in health and disease. 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.

Senoo N, Chinthapalli DK, Baile MG, Golla VK, Saha B, Oluwole AO, Ogunbona OB, Saba JA, Munteanu T, Valdez Y, Whited K, Sheridan MS, Chorev D, Alder NN, May ER, Robinson CV, Claypool SM. Functional diversity among cardiolipin binding sites on the mitochondrial ADP/ATP carrier. EMBO J. 2024 Jun 5. doi: 10.1038/s44318-024-00132-2.