A direct consequence of the ,Mitochondrial RenaissanceŠ which has occurred in the biological sciences over the past 15 years is the recognition that mitochondria do not simply serve as the primary source of ATP in the cell, but they also serve as centralized focal points of cellular signaling, facilitating an assortment of cellular processes from growth and differentiation to apoptosis using a variety of intermediates (see diagram below).
The primary research focus of my laboratory is centered on the role of lipids and reactive oxygen species (ROS) in altering mitochondrial function, and in how the mitochondria uses these and other molecular intermediates to communicate with the rest of the cell, particularly the nucleus, in normal physiological states as well as disease. An increased understanding of these processes, coupled with improvements in mitochondrial-targeted pharmaceutical chemistry, will allow a new era to become realized where mitochondria are a viable therapeutic target in disease management.
We have recently established a strong and dynamic collaboration with cardiac surgeons here at the East Carolina Heart Institute (ECHI), and this has allowed us to obtain human cardiac tissue biopsies from patients at time of surgery. Using a number of techniques to study mitochondrial function at the subcellular (i.e. organelle) and whole cell ‹ level in this tissue, we have recently uncovered a number of interesting mitochondrial abnormalities present in patients with type 2 diabetes (Anderson et al, J Amer Coll Cardiol, Vol. 54 No. 20, 1891-1898 (2009). Current research projects in my lab have both Clinical and Basic science research aspects. Having on-going projects rooted in both of these disciplines allows us to address fundamental questions about cellular physiology yet still keep our attention on the importance of these questions in a clinically relevant context. Research in our lab is supported by industry (GlaxoSmithKline) and federal (NIH) sponsors.
1. Role of n-3 poly-unsaturated fatty acids (PUFAs) in modulating cardiac mitochondrial function in health and disease (Basic and Clinical research components)
2. Relationship between cardiac glutathione redox chemistry and post-operative atrial fibrillation (Clinical Science)
3. Impact of cytokines such as TNFα and adiponectin on mitochondrial function in cardiomyocytes (human cardiomyocytes and rodent models)
4. Role of cardiac mitochondria in mediating cytokine signals from plasma membrane à nucleus (human cardiomyocytes and rodent models)
5. Molecular intermediates that mediate the cross-talk between mitochondria and nucleus during cellular stress (human cardiomyocytes and rodent models)
Anderson EJ, Thayne K, Harris M, Carraway K, Shaikh, SR Aldehyde stress and up-regulation of Nrf2-mediated antioxidant systems accompany functional adaptations in cardiac mitochondria from mice fed n-3 polyunsaturated fatty acids. Biochem J 2012
Anderson EJ, Rodriquez E, Anderson CA, Thayne K, Chitwood WR, Kyson AP, Increased propensity for cell death in diabetic human heart is mediated by mitochondrial-dependent pathways. Am J Physiol Heart Circ Physiol 2010
Kane DA*, Anderson EJ*, Woodlief TL, Price III JW, Bikman BJ, Cortright, RN and Neufer PD, Metformin Selectively Attenuates Mitochondrial H2O2 Emission without Affecting Respiratory Capacity in Skeletal Muscle of Obese Rats. Free Rad Biol Med 2010
Anderson EJ, Kypson A, Rodriguez E, Anderson CA, Lehr EJ, Neufer PD, Substrate-Specific Derangements in Mitochondrial Metabolism and Redox Balance in the Atrium of the Type 2 Diabetic Human Heart, J Amer Coll Cardiol 2009
Brown DA, Aon MA, Frasier CR, Sloan RC, Maloney AH, Anderson EJ, O‰Rourke B, Cardiac Arrhythmias Induced by Glutathione Oxidation can be Inhibited by Preventing Mitochondrial Depolarization, J Mol Cell Cardiol 2010
Bikman BT, Zheng D, Kane DA, Anderson EJ, Woodlief TL, Price JW, Dohm GL, Neufer PD and Cortright RN, Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKβ Action in a Fiber-type Specific Manner, J Obesity 2009
Anderson EJ, LustigME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price III JW, Kang L, Ravinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DW, and Neufer PD. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 2009
Anderson EJ, Yamazaki H, and Neufer PD. Induction of endogenous UCP3 suppresses mitochondrial oxidant emission during fatty-acid supported respiration in skeletal muscle. J Biol Chem 2007
Anderson EJ, and Neufer PD. Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation. Am J Physiol-Cell Physiol 290 844-851 (2006)
Wu JJ, Roth R, Anderson EJ, Hong E-G, Lee M-K, Choi CS, Neufer PD, Shulman GI, Kim JK, and Bennett AM. Mice Lacking MAP Kinase Phosphatase-1 have enhanced mitogen-activated protein (MAP) kinase activity and resistance to diet-induced obesity. Cell Metab 4(1) 61-73 (2006)
Green, AL, Anderson EJ, and Brooker, RJ. A revised model for the structure and function of the lactose permease. Evidence that a face on transmembrane segment 2 is important for conformational changes. J Biol Chem 275, 23240-23246 (2000)