Mito-communications

Abstract

The correlation of mitochondrial (mt) anomalies with human disease in general, and neurodegenerative disorders in particular, is extensive. Here, we summarize the work of one particularly interesting study utilizing human mtDNA variants to examine neurodegenerative disorders. Blohkin et al. (2008) ask whether mt copy number anomalies are pathology-related to multiple sclerosis (MS). Previous work had determined that there is an age-dependent effect on the mtDNA copy number in cells that are cytochrome oxidase negative (COX 2). In the study reported in the Journal of Molecular Neurosciences the authors examined the correlation of mtDNA copy number with tissue degeneration associated with inflammatory demyelination of COX 2 and COX þ single glial cells associatedwithMS.Theyused real-time PCR of an ND1/18s rDNA amplification system (the 18S rDNA component of the amplification serves as a control or calibrator) to quantify the copy number of mtDNA molecules in several types of postmortem tissues. The tissues examined were normal-appearing gray matter (NAGM) and normalappearing white matter (NAWM) regions and chronic active plaques of MS patients. The authors determined that there is a significantly higher mtDNA copy number in neurons of NAGM than in cells of other MS brain regions.Anage-related decline inmtDNAcopynumber was also observed in neurons of both MS patients and controls. The results of the study exclude a change in copy number as a factor in plaque formation in MS patients. However, the authors suggest that a compensatory replication ofmtDNAormt biosynthesis occurs with neuroaxonal loss in MS. The authors suggest that some features of late-onset MS may be explained by the age-related decline of mtDNA copy number. We direct the reader to Yang et al. (2008) for a recent review of the role of mtDNA anomalies in neurodegenerative disorders.