conditions have been linked to loss of mitochondrial mem- brane function and increases in membrane permeability.


How Damaged Mitochon- dria Wreak Havoc


Damage to mitochondrial com- ponents, especially the delicate inner mitochondrial membrane, leads to the release of toxic proteins, including caspases and other enzymes. These pro- teins are normally confined in the mitochondria, but once released these pro- teins go through several steps that trigger the formation of a potent inflammatory molecu- lar complex called an inflam- masome. New evidence has placed inflammasomes at the center stage of complex diseas- es like metabolic syndrome and cancer, as well as the regulation of the microbial ecology in the intestine and the production


of ATP.13, 14, 15, 16, 17, 18, 19


Inflam-


masomes are regarded by some scientists as ‘guardians of the body’ because of the way they orchestrate host defenses and their role in the pathogenesis of inflammatory diseases.20


Once the inner membrane of


lation; biosynthesis of key mol- ecules, including heme and cer- tain steroids as well as in many catabolic energy relevant path- ways, such as the β-oxidation of fatty acids; and regulation of calcium homeostasis.21


The integrity of mitochondrial membranes is critical to cell function and energy metabolism. This membrane is the frontier between cell survival and death.


the mitochondria is damaged, its core ability to produce en- ergy in the form of ATP and to maintain optimal mitochondri- al nutrient uptake and utiliza- tion necessary for ATP produc- tion are impaired. The result is perceived as persistent fatigue.


Mitochondria are also respon- sible for many metabolic cir- cuits and signaling pathways. Just a few examples of these include: oxidative phosphory-


Garth L. Nicolson PhD, a Nobel Prize Nominee, is a world-renowned authority on cellular medicine and chronic illnesses, with over 600 publications and nine US patents. Dr. Nicolson conducted and published the seminal research on the lipid bi-layer fluid mosaic model of the human cell membrane. He has served as editor of six medical journals and associate editor of 29 medical books and journals. He was Professor and Chairman of the Tumor Biology department at the University of Texas MD Anderson Cancer Center,


In addition, the immune sys- tem is stimulated by molecular byproducts of mitochondrial dam- age to produce inflam- matory cytokines. If inappropriately regu- lated, these cytokines then sustain and even


promote local and systemic in- flammation in a ‘feed-forward’ cycle of inflammatory messen- gers. Once the mucosal innate immune system is switched on to high-alert by the inflam- masome, GI bacteria become involved in this process, and the local specialized sensors become hyper-responsive to bacterial triggers from the gas- trointestinal tract – even from previously tolerated bacte-


and Professor of Comparative Biology at Texas A&M University. Dr. Nicolson was awarded Honorary Colonel of the US Army Special Forces and Honorary US Navy Seal for his work on veteran's illnesses. His research includes chronic infections, chronic fatigue syndrome, fibromyalgia, Lyme disease, rheumatoid arthritis, Gulf War illness, and various autoimmune diseases. Dr. Nicolson is President and CEO of the Institute for Molecular Medicine in Huntington Beach, California.


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