Mohammed Akbar, Musthafa M. Essa, Byoung-Joon Song and Mohammed A.S. Khan Pages 93 - 98 ( 6 )
Background: Mitochondria are critically important in providing cellular energy ATP. They also play important roles in anti-oxidant defense, fat oxidation, intermediary metabolism and cell death processes. It is well-established that mitochondrial functions are suppressed through nitroxidative stress when living cells or organisms are exposed to potentially toxic agents including alcohol, high fat diets, smoking and certain drugs or in many pathophysiological states. Under elevated nitroxidative stress, cellular macromolecules proteins, DNA, and lipids can undergo different types of modification, usually leading to disruption of their normal, sometimes critical, physiological functions. Recent reports have also indicated that many mitochondrial proteins are suppressed through various post-translational modifications (PTMs), contributing to mitochondrial dysfunction and cell death, as observed in many distinct neurodegenerative diseases including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD), alcoholic dementia, and ischemia-reperfusion related brain injury (stroke).
Methods: In this review article, we have described an overview of the sensitive methods we developed for the detection of PTMs of mitochondrial proteins. And by using in vitro AD mouse model, we demonstrated that dietary supplements can alleviate the disease condition by inhibiting pro-inflammatory cytokines and mediating protective effects.
Results: Here, we have discussed the simple methods that we developed in our lab for the detection of PTMs of mitochondrial proteins, and have shown that how PTMs affect the normal cellular functions. Secondly, we have also discussed the role of natural antioxidants, including plant flavonoids and polyphenols that can inhibit or delay the formation of reactive oxygen/nitrogen species, prevent the mitochondrial dysfunction and apoptosis in various neurodegenerative diseases.
Conclusion: In conclusion, we made an attempt to give an overview on the PTMs of mitochondrial proteins and their importance in understanding the role of mitochondrial dysfunction and apoptosis in neurodegenerative diseases. Furthermore, we described the PTMs (oxidation, nitration, phosphorylation, etc.) of mitochondrial proteins that may play an important role in mitochondrial dysfunction and promote neuro-degeneration. We also concluded that ingesting healthy diets combined with physical exercise may restore normal mitochondrial functions (Fig. 1). Furthermore, a better understanding of the mitochondrial dynamics as well as nitroxidative stress may lead to the development of new translational approaches for the prevention and treatment of mitochondria-related neurodegenerative diseases.
Antioxidant, apoptosis, dietary supplement; mitochondrial dysfunction, neurodegeneration, nitroxidative stress, post-translational modification.
Section of Molecular Pharmacology and Toxicology, LMBB, NIAAA, NIH, Bethesda, MD -20892. USA.