| For a long time it was assumed that mitochondria were highly efficient energy factories for the cell. However, to the contrary, it has been conclusively demonstrated that, other than being major producers of ATP in the cell, they generate superoxide (O2·-) as a byproduct of the respiratory chain. In neurodegenereative diseases, stroke or ischemic injury, and exposure to mitochondrial toxins, reactive species can overwhelm the cellular antioxidant defenses and induce oxidative stress. Oxidative stress can induce mitochondrial DNA (mtDNA) damage, lipid peroxidation, and structural alterations of important proteins. Such changes result in mitochondrial bioenergetic restriction and can induce cell death pathways. Tissues with high energy requirements such as brain, cardiac and skeletal muscles are particularly vulnerable to such assaults that create a devastating and vicious cycle of reactive oxygen species (ROS) production and macromolecule damage. There is a concerted effort to understand mitochondrial energy metabolism and maintenance. A clear understanding of such processes may be useful in developing biomarkers for mitochondrial dysfunction, and identify novel pharmacological or biological targets for various interventions to restore mitochondrial integrity in diseases. To this end, we have studied metabolic and antioxidant protein alterations in a U87 cell line challenged with mtDNA depletion. Since mtDNA damage or deletion is noted in aging brain, neurodegenerative diseases, mitochondrial myopathies, and nucleoside analogue-based HIV therapy, we hypothesized that such cell culture models can be invaluable in molecular studies that may have important diagnostic and clinical implications and applications. |
