Cardiolipin links mitochondrial lipid synthesis to TCA cycle function - Implications for Barth syndrome

Miriam L. Greenberg is a Professor in the Department of Biological Sciences at Wayne State University.  She holds a BA in Biology from Reed College, an MS in Microbiology from Loyola University, and a PhD in Genetics from Albert Einstein College of Medicine. She carried out her postdoctoral work in Molecular Biology at Harvard University. She has held visiting professorships at Utrecht University in the Netherlands, Ben Gurion University in Israel, and the Weizmann Institute of Science in Israel.  She currently holds an ‘extraordinary Visiting Professorship’ at the Weizmann Institute of Science. Her research aims to understand the specialized functions of phospholipids, specifically focusing on elucidating the functions of the mitochondrial lipid cardiolipin and on characterizing the mechanisms underlying regulation of synthesis of the lipid precursor, inositol. These studies have implications for understanding the pathology underlying the cardiovascular disorder, Barth syndrome, and the therapeutic mechanisms of action of drugs used to treat bipolar disorder. She is currently a member of the Scientific and Medical Advisory Board of the Barth Syndrome Foundation and the editorial board of Chemistry and Physics of Lipids.  

Cardiolipin (CL), the signature phospholipid of mitochondria, is crucial not only for mitochondrial function but also for a plethora of cellular processes that are not associated with mitochondrial bioenergetics. The de novo synthesis of CL is followed by a remodeling cycle of deacylation (removal of a fatty acid) and reacylation. Specific fatty acyl composition is acquired during this process, and remodeled CL contains predominantly unsaturated fatty acids.  The importance of CL remodeling is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), caused by mutations in tafazzin, the enzyme that reacylates CL.  Although the clinical phenotypes of BTHS point to mitochondrial bioenergetic defects, the molecular basis whereby CL deficiency leads to the pathology is not understood.  Our recent studies indicate that CL is required for optimal activity of the mitochondrial ‘gatekeeper enzyme’ pyruvate dehydrogenase.  CL deficiency results in decreased synthesis of acetyl-CoA and perturbation of the TCA cycle.  Anaplerotic pathways that replenish acetyl-CoA and TCA cycle intermediates are essential for viability of CL-deficient cells.  These findings link the mitochondrial membrane lipid CL to the energy metabolism pathways in the matrix and suggest a mechanism underlying the pathology in BTHS.

This seminar will NOT be livestreamed or recorded.