Abstract

Beyond energy, the mitochondrion is also a powerhouse of phospholipid biosynthesis. The mitochondrion is the home for one of the two major phosphatidylethanolamine (PE) biosynthetic pathways in cells and is the sole site of production of the dimeric phospholipid, cardiolipin (CL). Mutations that specifically impair normal mitochondrial phospholipid metabolism represent an emerging class of mitochondrial disease. Barth syndrome, an X-linked childhood cardiomyopathy caused by mutations in the gene that encodes the CL remodeling enzyme TAZ , was the founding member of this new category of human disease. More recently, mutations in the gene that encodes the mitochondrial enzyme that makes PE, PISD , have been determined to cause a novel mitochondrial chaperonopathy. Thus, human genetics has made it clear that normal mitochondrial phospholipid metabolism as a whole is clinically important. Our goal is to obtain a detailed mechanistic understanding of how individual phospholipids support the myriad of proteins, protein complexes, and functions that occur within and across mitochondrial membranes. Such information is needed to fully understand the numerous roles played by phospholipids in both healthy and disease states.