Oxidative Stress and Mitochondrial Dysfunction: Key Players in CFS?

Understanding CFS | 21. Jul, 2011 by | 10 Comments

By Dikoma C. Shungu, Ph.D., professor of physics in radiology, psychiatry, and physiology and biophysics at the Weill Cornell College of Cornell University

For the July 15 edition of “Five Picks,” rather than one pick, I made two. Here, I explain in greater detail why these two papers form a really nice package:

Zeevalk GD, Bernard LP, Song C, Gluck M, Ehrhart J. Mitochondrial inhibition and oxidative stress: reciprocating players in neurodegeneration. Antioxidant & Redox Signaling 2005; 7: 1117-1139. (A free abstract of this article and its first page are available at: http://www.liebertonline.com/doi/abs/10.1089/ars.2005.7.1117)

Zeevalk GD, Razmpour R, Bernard LP. Glutathione and Parkinson’s disease: is this the elephant in the room? Biomedicine & Pharmacotherapy 2008, 62: 236-249. ((A free abstract of this article is available at http://www.ncbi.nlm.nih.gov/pubmed/18400456)

I have been turning to these two papers with increasing frequency since I became interested in investigating the possibility that oxidative stress and mitochondrial dysfunction may be key players in CFS pathophysiology, and that glutathione (GSH), a small but ubiquitous tripeptide, might be the most important natural defense against these two disease-causing events. And why would all of this come about? Well, because there is no free lunch, even in nature!


Model presented by Dr. Shungu in webinar (see below)

The evolutionary development of the mitochondria as the primary “factory” for the production of chemical energy needed to power all activity in living cells did not come without a price. Up to five percent  of all oxygen molecules entering the mitochondrial electron transfer chain can acquire an electron to form the superoxide free radical, which can be converted enzymatically or non-enzymatically to various powerful reactive oxygen or nitrogen species (ROS/RNS). Once formed, these ROS/RNS would do what they are supposed to do, which is to react indiscriminately with proteins, membrane lipids, nucleic acids or DNA, causing, among other terrible things, mitochondrial dysfunction (this will cause the production of yet more ROS/RNS, leading to a self-sustaining vicious cycle), neurodegeneration and cell death. Hence one of life’s great paradoxes: the mitochondrion, one of its most important organelles, as a ticking time bomb that must be constantly defused by neutralizing the effects of ROS/RNS that it generates in the process of producing the chemical energy required to sustain life. As a way out of this conundrum, the cell was equipped early on with an effective antioxidant defense system, of which glutathione is the most abundant and one of the most important components, to protect the organism against ROS/RNS (i.e., oxidant) attacks and their potential to cause oxidative stress damage, mitochondrial dysfunction and cellular degeneration and death. It is thus not surprising that GSH deficiency has been associated with a wide range of human diseases, including aging-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, fatigue syndromes, as well as normal aging.

If you find all of that fascinating, then you should first turn to the 2005 paper by Zeevalk and colleagues in which they show that if neurodegeneration were a coin, mitochondrial dysfunction would be on one of its faces, while oxidative stress would be on the other, and that in addition to their role in causing neurodegeneration, the two processes are constantly amplifying each other. You would then turn to their 2008 paper in which they make the compelling case that the most effective way to prevent oxidative stress and/or mitochondrial dysfunction from happening and causing all kinds of health problems is to maintain adequate reserves of glutathione (GSH), and then they evaluate a number of strategies for increasing brain GSH reserves since this compound does not cross the blood-brain barrier and thus cannot be increased by simply taking daily supplements.

Dikoma-Shungu-SolveCFS-269x300Dikoma C. Shungu, Ph.D.,  is a professor of physics in radiology, psychiatry, and physiology and biophysics at the Weill Cornell College of Cornell University. He is also chief, of the Laboratory for Advanced MRS Research of the Citigroup Biomedical Imaging Center at Weill Cornell. The Solve ME/CFS Initiative has funded Dr. Shungu’s research on brain lactate levels in CFS. To read more about his study, please read “Brain Power,”this article from NY-Presbyterian Hospital’s magazine, or view the recording of a webinar, “Expanding Research: Building On Your Investment,” featuring Dr. Shungu and other investigators supported by the Solve ME/CFS Initiative. Dr. Shungu’s most recent CFS-related peer-reviewed publication is “Increased ventricular lactate in chronic fatigue syndrome measured by H MRS imaging at 3.0 T. II: comparison with major depressive disorder.” NMR in Biomedicine. July 2010.

July 21, 2011