Anne N. Murphy
Associate Professor (Adjunct), Department of Pharmacology
Ph.D., The George Washington University School of Medicine and Health Sciences, Washington, D.C.
Alterations in mitochondrial metabolism and ATP production are associated with a wide variety of conditions including neurodegenerative disorders, metabolic disease, ischemic injury, and cancer. We aim to identify therapeutic strategies that improve metabolic function, with a current focus on Alzheimer’s Disease. The brain requires an enormous amount of energy for the specialized tasks of neurotransmission, and a defect in energy metabolism exists in the brains of Alzheimer’s Disease patients. By targeting specific mitochondrial proteins, we believe that a beneficial response can be elicited that improves brain energy metabolism. One mitochondrial protein complex on which we focus is a recently discovered transporter in mitochondria, the mitochondrial pyruvate carrier, which acts as a central hub of metabolism. Other efforts in the lab focus on the development methodologies that facilitate mitochondrial research. We combine measurements of mitochondrial oxygen consumption on intact or permeabilized cells and isolated mitochondria with metabolic flux analysis and metabolite measurements to build a comprehensive picture of cell energy metabolism.
• Divakaruni AS, Wiley SE, Rogers GW, Andreyev AY, Petrosyan S, Loviscach M, Wall EA, Yadava N, Heuck AP, Ferrick DA, Henry RR, McDonald WG, Colca JR, Simon MI, Ciaraldi TP, Murphy AN (2013) Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier. Proc Natl Acad Sci USA. 110(14):5422-7.
• Vacanti NM, Divakaruni AS, Green CR, Parker SJ, Henry RR, Ciaraldi TP, Murphy AN, and Metallo CM (2014) Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier, Molecular Cell 56:425-435.
• Yamazaki KG, Andreyev A, Ortiz-Vilchis P, Petrosyan S, Divakaruni AS, Wiley SE, De La Fuente C, Perkins G, Ceballos G, Villarreal F, Murphy AN. (2014) Intravenous (-)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function. Int J Cardiol 175(2):297-306.
• Wiley SE, Andreyev AY, Divakaruni AS, Karisch R, Perkins G, Wall EA, van der Geer P, Chen Y-F, Tsai T-F, Simon MI, Neel BG, Dixon JE, Murphy AN (2013) Wolfram Syndrome protein, Miner1, regulates sulphhydryl redox status, the unfolded protein response and Ca2+ homeostasis. EMBO Mol Med 5(6):904-18.
• Rogers, G.W., Brand, M.D., Petrosyan, S., Ashok, D., Elorza, A.A., Ferrick, D.A. and Murphy, A.N. (2011) High throughput microplate respiratory measurements using minimal quantities of isolated mitochondria. 6(7): e21746. doi:10.1371/journal.pone.0021746.