Mitochondrial involvement in brain function and dysfunction: Relevance to aging, neurodegenerative disorders and longevity

It is becoming increasingly evident that the mitochondrial genome may play a key role in neurodegenerative diseases. Mitochondrial dysfunction is char acteristic of several neurodegenerative disorders, and evidence for mitocho ndria being a site of damage in neurodegenerative disorders is partially ba sed on decreases in respiratory chain complex activities in Parkinson's dis ease. Alzheimer's disease, and Huntington's disease. Such defects in respir atory complex activities, possibly associated with oxidant/antioxidant bala nce perturbation. are thought to underlie defects in energy metabolism and induce cellular degeneration. Efficient functioning of maintenance and repa ir process seems to be crucial for both survival and physical quality of li fe. This is accomplished by a complex network of the so-called longevity as surance processes. which are composed of genes termed vitagenes. A promisin g approach for the identification of critical gerontogenic processes is rep resented by the hormesis-like positive effect of stress, In the present rev iew, we discuss the role of energy thresholds in brain mitochondria and the ir implications in neurodegeneration. We then review the evidence for the r ole of oxidative stress in modulating the effects of mitochondrial DNA muta tions on brain age-related disorders and also discuss new approaches for in vestigating the mechanisms of lifetime survival and longevity.