et al. Clonally expanded mitochondrial DNA deletions within the choroid
plexus in multiple sclerosis. Acta Neuropathol. 2012 Jun 12.
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
(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.
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
The mitochondria are the power houses of cells and create energy for the
cell. In MS we think that there is a mitochondrial deficit that results
in less energy being produced from the cell, this could because it has to work harder
when nerves are demyelinated. This may make the nerve vulnerable to damage and death as we have discussed in 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