Biodefense by Protecting Mitochondria

Amanda Claire Milstein, Rasika Vartak and Yidong Bai^*

Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA

*Corresponding Author:

Yidong Bai
Department of Cellular and Structural Biology
University of Texas Health Science Center at San Antonio
7703 Floyd Curl Drive, San Antonio, Texas 78229, USA
Tel: 1 210 567 0561
Fax: 1 210 567 3803
E-mail: baiy@uthscsa.edu

Received Date: September 21, 2012; Accepted Date: September 22, 2012; Published Date: September 25, 2012

Citation: Milstein AC, Vartak R, Bai Y (2012) Biodefense by Protecting Mitochondria. J Bioterr Biodef 3:e104 doi: 10.4172/2157-2526.1000e104

Copyright: © 2012 Milstein AC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Bioterrorism & Biodefense

Nuclear weaponry was and remains the most significant threat to public health during war. However, during these times of covert terrorist attacks, a new and potentially deadly form of warfare is coming to light. As modern science has progressed, the affordability of producing chemical and biological agents on mass scale has made them an attractive mode of attack and it is now of paramount importance to devise ways that can limit the dangers posed by these agents.

One of the major discoveries in recent years has been the underlying importance of mitochondria in pathogenesis of a variety of diseases and disorders. Mitochondrial dysfunction has been associated with cancer, neurodegenerative disorders as well as aging. The mitochondrion is responsible for producing massive quantities of ATP (energy) for the cell. When a prokaryote (very primitive single-celled organisms) takes in a molecule of glucose, it can only use it to produce about 4 molecules of ATP. But the mitochondria found in eukaryotic cells churn out about 38 molecules of ATP for every molecule of glucose. This near ten-fold increase in ATP production has allowed cells to differentiate and specialize. This single adaptation has led to the rise of profoundly complex multicellular organisms like us. As such, we rely on it. Without a healthy, functioning mitochondrial network, our cells break down rapidly.

There’s a good reason why mitochondria are so singularly important for cell survival. Unlike other organelles, mitochondria originated as a separate organism, living symbiotically within other cells. The strongest piece of evidence we have to trace this origin is the mitochondrial genome, which is yet another prime target for attack by external toxins. DNA damage has lasting consequences, and while it is small, the mitochondrial genome encodes genes for the key group of proteins that make up the electron transport chain. Mutations in these regions can cripple cellular respiration beyond repair.

A second vitally important process that the mitochondrial network oversees is called apoptosis. This is a form of programmed cell death, wherein a cell that is extremely damaged “commits suicide,” so that the organism can go on unhindered by its malfunctions. The apoptotic pathway plays a large role in cancer research and is a logical target for toxins meant to induce cell death. So, even if mitochondria are not the main target for many biological agents, the cell death they cause is invariably controlled by the mitochondria. This makes the mitochondrial network an attractive target for protection against the secondary and long term effects of these agents.

Another technique by which the mitochondrial network could be crippled or damaged is the induction of reactive oxygen species. ROS are molecules of oxygen with unpaired electrons that make them highly reactive. They are mutagenic compounds that can cause extensive protein and DNA damage and ultimately cell death. Many drugs that directly inhibit portions of the electron transport chain also increase the production of ROS. Cyanide is an example of a potent toxin that shuts off respiration and ATP production, in this case by inhibiting respiratory Complex IV. Arsenic, commonly used in pesticides, in very small doses can inhibit ATP synthesis by inhibiting formation of acetyl CoA, in addition to producing excess ROS [1]. Rotenone and paraquat, two other chemicals commonly found in pesticides, can cause mitochondrial dysfunction by inhibiting respiratory complex I and causing increase in ROS. Both chemicals have been linked to Parkinsonism in animal models [2]. All this evidence validates the use of mitochondria as an appropriate target for protection against chemical and biological warfare.

The question remains, however, whether there is any way to actually protect mitochondria and therefore limit the effects of these various agents. Recent strides in mitochondrial research have yielded some positive results. Studies have shown that use of some powerful antioxidants can help limit the damage done by reactive oxygen and nitrogen species. Melatonin has been reported to have a broadly protective effect for mitochondria. It is a very strong anti-oxidant and has been known to decrease ROS and improve mitochondrial membrane potential. It is also known to increase the activities of respiratory complexes I and IV in the electron transport chain. Whether melatonin can reverse the effects of mitochondrial dysfunction is a fascinating area of research [3]. Interestingly, melatonin has also been found to be protective against detrimental effects of gamma irradiation [4]. Another substance that has gained importance recently is taurine, another anti-oxidant that is thought to protect against arsenic poisoning [5]. It would be worthwhile to research the protective effects of taurine against other poisons.

Other studies have been done to determine what kind of a role the signaling molecule PGC-1α, which is a key regulator of mitochondrial biogenesis, could play in preventing or repairing oxidative damage in the mitochondrial network [6]. Boosting mitochondrial biogenesis pre-emptively through PGC-1α has had a positive effect in aging and mitochondrial disorders [7]. This area looks promising, and merits further study, especially with regard to biodefensive applications.

Research into protective anti-oxidant compounds is the first step in a larger attempt to treat what was previously considered untreatable damage. Mitochondrial research on its own can sometimes feel far-removed from practical health concerns, but these fascinating organelles are at the heart of our most basic functions. Further research into protecting mitochondrial health is absolutely necessary for combating a wide variety of diseases, toxic effects and other environmental irritants that may pose a threat to public health.

References

1. Stone R (2008) Food safety. Arsenic and paddy rice: a neglected cancer risk? Science 321: 184-185.
2. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, et al. (2011) Rotenone, paraquat, and Parkinson's disease. Environ Health Perspect 119: 866-872.
3. Dragicevic N, Copes N, O'Neal-Moffitt G, Jin J, Buzzeo R, et al. (2011) Melatonin treatment restores mitochondrial function in Alzheimer's mice: a mitochondrial protective role of melatonin membrane receptor signaling. J Pineal Res 51: 75-86.
4. Vijayalaxmi, Reiter RJ, Herman TS, Meltz ML (1998) Melatonin reduces gamma radiation-induced primary DNA damage in human blood lymphocytes. Mutat Res 397: 203-208.
5. Das J, Ghosh J, Manna P, Sil PC (2010) Protective Role of Taurine against Arsenic-Induced Mitochondria-Dependent Hepatic Apoptosis via the Inhibition of PKCd-JNK Pathway. PLoS ONE 5: e12602.
6. Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT (2009) Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA 106: 20405-20410.
7. Srivastava S, Diaz F, Iommarini L, Aure K, Lombes A, et al. (2009) PGC-1alpha/beta induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders. Hum Mol Genet 18: 1805-1812.