A direct consequence of the
“Mitochondrial Renaissance” 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).
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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.
Research interests
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 ŕ 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, 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)
