Campbell et al. Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis. Acta Neuropathol. 2012 Jun 12.
Mitochondrial DNA deletions (mtDNA) have been implicated in the pathogenesis of Alzheimer's disease (AD), MS and Parkinson's disease (PD), as well as ageing. Clonal expansion = replication of mtDNA is the process by which a mutant mtDNA molecule increases to high levels within a single cell containing both wild-type and mutant mtDNA. Unlike in AD and PD, the diffuse inflammatory process in MS involves the choroid plexus, and mitochondria are exposed to reactive oxygen and nitrogen species over a prolonged period.
The extent of respiratory enzyme deficiency and mtDNA at a single cell level within choroid plexus epithelial cells in MS as well as in AD, PD and controls. The respiratory enzyme-deficient (lacking complex IV and with intact complex II activity) cells were more prevalent within the choroid plexus in AD, MS and PD compared with controls. The main catalytic subunit of complex IV (subunit-I of cytochrome c oxidase) was lacking in significantly more respiratory enzyme-deficient cells in MS compared with AD, PD and controls. The single cell analysis showed a fourfold increase in the percentage of respiratory enzyme-deficient choroid plexus epithelial cells harbouring clonally expanded mtDNA in MS. Our findings establish clonal expansion of mtDNA as a feature relatively more prominent within the choroid plexus epithelium in MS than AD, PD or controls. We propose clonal expansion of mtDNA as a molecular link between inflammation and part of a delayed cellular energy failure in MS.
Eukayote is just something a term to distinguish this from prokaryotic which is bacteria cell
Mitochondrial DNA (mtDNA) is the DNA located in organelles called mitochondria, structures that convert the chemical energy from food into a form of energy (adenosine triphosphate (ATP)) that cells can use. Most other DNA present in cells of mammals and humans is found in the cell nucleus. In most species, including humans, mtDNA is inherited solely from the mother.
previous posts. For example it blocks some energy dependent ion pumps that can lead to the accumulation of toxins into cells, which cause them to die
This study found expansions of mtDNA which is an indicator of damage and in this study there was more evidence of damage in MS compared to Alzheimers or Parkinsons disease in the corpus callossum, which is the nerve tract going from the left and right sides of the brain. You might expect this as Alzheimers and Parkinsons disease may be more likely to affect different areas of the brain.
The production of energy required the sequential action of enzymes called complex I, II, III, IV, V called the respiratory chain enzymes. In this study there was a change in complex IV. Is this a cause of pathology or a consequence of the nerves in the choroid plexus having to work harder. This is difficult to know. This study just gives another idea of how damage can occur in progressive MS, it is not the only one
van Horssen J, Witte M, Ciccarelli O. The role of mitochondria in axonal degeneration and tissue repair in MS. Mult Scler. 2012 Jun 21. [Epub ahead of print]