Professor Dikoma C. Shungu: Oxidative Stress and Mitochondrial Dysfunction: Key Players in CFS

Professor Dikoma C. Shungu, Ph.D., 21. JUL, 2011:

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!

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 ... Read more>>