Search:

Product Information All Elsevier Sites   Advanced Product Search
SiteStat.jsp
BBA - General Subjects - Redox Control of Cell Function

Christopher Horst LilligBBA - General Subjects
The Impact of Host Iron Homeostasis on Disease
Edited by J.R. Connor and A.J. Ghio

External linkVolume 1790, Issue 7,  Pages 581-740 (July 2009)

Iron is an essential nutrient utilized in every aspect of cell function. There are few organisms that do not have an absolute requirement for this metal. This complete dependence of life on iron availability is particularly true in aerobic systems, which derive energy through an oxidation of hydrocarbons to carbon dioxide with molecular oxygen (O2) functioning as the final electron acceptor. Ground state O2 exists as a triplet and this presents a kinetic block to its reactions with singlet molecules. To overcome this singlet-triplet reaction barrier, transfer of electrons to O2 is catalyzed by iron. Iron was selected in molecular evolution to support such reactions as a result of its interactions with O2, its tendencies toward complex formation (coordination), the variability of the redox potential after complexation, and its abundance. Those same chemical properties that allow iron to function as a catalyst in the reactions of molecular oxygen can present a threat to living systems via a generation of O2-based free radicals. Therefore, while an organism must obtain iron to catalyze homeostatic and synthetic functions, oxidants generated by the metal have a capacity to damage biological molecules and present a threat to life. Accordingly, life was designed to exist at the very interface of iron-deficiency and iron-sufficiency. This is similar to oxygen, which is utilized in the mitochondria at levels approaching the edge of hypoxia (i.e., 1 to 5 mm Hg). The alternative to this approach of employing iron and oxygen is damaging oxidative stress.

If iron and oxygen equilibriums are positioned at the focus of aerobic life, then a disruption in the homeostasis of both is anticipated with many injuries to that organism. Indeed, there are now too many human diseases demonstrating some disequilibrium in iron to provide a brief list as done previously in both textbooks and journal articles. This special issue of BBA General Subjects addresses this large number of human diseases now recognized to involve disruptions in iron homeostasis. Many more such injuries will be identified in the near future and the articles included in this issue reflect a rapidly evolving field.

 

Christopher Horst LilligJames R. Connor

Dr. James R. Connor received a Bachelor of Arts in psychology in 1975 from Thomas More College (Ft. Mitchell, KY), a Master of Science from Wright State University (Dayton OH) in physiology and a Ph.D. in anatomy from the University of California, Berkeley, in 1981. Dr. Connor's postdoctoral training was at Boston University School of Medicine (1981–1983) where he studied with Dr. Alan Peters. In 1983, Dr. Connor accepted an appointment as a research scientist in the Spinal Cord Injury Research Unit at the Veterans’ Administration Hospital in Washington D.C. and as an assistant professor in the Department of Physiology at George Washington University School of Medicine. In 1987, he joined the faculty at the Penn State University College of Medicine as an assistant professor in the Department of Anatomy and became a full professor in 1996. In 2004, Connor moved to the Department of Neurosurgery as Vice-Chair for Research. In 2007, he was named a University Distinguished Professor of Penn State University. He is the Director of the G.M. Leader Family Laboratory and Co-Director of Neuro-oncology Research for the Penn State Cancer Institute.

Dr. Connor's research program has enjoyed continuous funding since 1985 from a number of funding agencies. Support for Dr. Connor's program has come from four agencies within the National Institutes of Health (NINDS, NIA, NIDDK, NICHD), the Veterans’ Administration, the National Multiple Sclerosis Society, American Federation for Aging Research, Alzheimer's Association, American Health Assistance Foundation, Muscular Dystrophy Association, and the Restless Legs Syndrome Foundation. Dr. Connor's research program is focused on understanding the mechanisms for regulation of iron in the brain. Connor's group pioneered the development of the field of iron in neurobiology. Connor and his team have identified the contribution of iron mismanagement in the brain to numerous neurological diseases such as Alzheimer's and Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, and more recently Restless Legs Syndrome. The demonstration by Connor's group that excess iron accumulates in the brain in Alzheimer's and Parkinson's has laid the groundwork for iron chelation therapy and antioxidant treatment strategies in these diseases. Connor's group has led studies into the contribution of mutations in a gene known as HFE to neurological disorders particularly in AD, ALS, and cancer. Dr. Connor has over 130 primary publications, over 30 review articles, and has edited two books: Metals and Oxidative Damage in Neurological Disorders and Redox Active Metals in Neurological Disorders.

In 1990, Dr. Connor was awarded the Samuel Hinkle Society Outstanding Young Investigator Award at the Penn State College of Medicine and in 2003 he was named Dean's Lecturer. He is the first person in the history of Penn State University to receive both of these awards from the College of Medicine. Dr. Connor was the President of the East Coast Iron Club from 2000–2002, and serves on the Scientific Advisory Boards for the Iron Disorders Institute and The Restless Legs Syndrome Foundation. For the latter foundation, he serves as Chair of the Scientific Advisory Board. He is a member of the GlaxoSmithKline Restless Legs Syndrome National Advisory Board and the Vifor (International) Inc. Board for Research Advancing Iron in Neurology (BRAIN) and a consultant for the International Copper Association. Connor is a member of the editorial boards for GLIA, Journal of Neuroscience Research, Current Neurovascular Research, Cerebrospinal Fluid Research, Neuroscience Journal and is an associate editor for the Journal of Alzheimer's Disease.
Back to top

Carsten BerndtAndrew J. Ghio

Andrew J. Ghio, MD, received his medical education from Boston University. After training in internal medicine and pulmonary/critical care medicine, he joined the faculty in the division of Pulmonary and Critical Care Medicine at Duke University in 1988. He continued his investigation as a Research Medical Officer in the Human Studies Division at the United States Environmental Protection Agency in Chapel Hill, North Carolina, from 1995 to present. Research and clinical interests include the role of iron in pulmonary disease. He is the author of numerous publications, which focus on the association of human injury and disease with altered iron homeostasis.

Back to top


  
Printer-friendly version   Printer-friendly version