Dr. Miriam Greenberg
Department of Biological Sciences
Wayne State University
Title: “Cardiolipin – mitochondrial phospholipid at the epicenter of energy metabolism”
Cardiolipin (CL) is a unique mitochondrial phospholipid that regulates many cellular functions and signaling pathways, both inside and outside of the mitochondria. The significance of CL in human health is apparent from clinical findings that perturbation of CL metabolism leads to the life-threatening disorder known as Barth syndrome.
The ubiquitous association of CL with energy transducing membranes is consistent with the role of this lipid in bioenergetics. In fact, CL synthesis and mitochondrial bioenergetics are inter-dependent, as CL synthesis is both required for and stimulated by oxidative phosphorylation. More recently, we have determined that, in addition to its function in bioenergetics, CL plays a key role in mitochondrial energy metabolism. Specifically, we have identified two mechanisms linking CL deficiency to perturbation of the TCA cycle. First, CL is required for optimal iron-sulfur biogenesis; therefore, activities of TCA cycle enzymes that require iron-sulfur co-factors are diminished in CL-deficient cells. Second, CL activates pyruvate dehydrogenase, and CL-deficiency results in decreased flux of glucose to acetyl-CoA.
We speculate that defects in energy metabolism may be physiological modifiers that account for the wide disparity of clinical phenotypes observed in Barth syndrome.
Host: Vishal Gohil
Location: 108 Biochemistry Building (Bldg#1507)