Mitochondria as Crucial Players in Demyelinated Axons: Lessons from Neuropathology and Experimental Demyelination

Figure 2

Mitochondrial dysfunction in MS and its models. Inflammation and the resulting toxic environment can have multiple effects on mitochondria including mtDNA damage (left arrow) and respiratory chain modifications (right arrow). Increased mtDNA copy number and mtDNA deletions have been observed in MS, which may be a related phenomenon. Actual respiratory chain defects are observed where all but complex II (blue) have both nuclear and mitochondrial DNA-encoded subunits. Defects include protein nitration affecting complexes I and IV observed in EAE, reduction in complex I activity in chronic lesions with reductions in complex I and III in nonlesional motor cortex. Complex IV activity is increased, along with mitochondrial mass, in chronic axons within nonpathological axons whilst a reduction is observed in pathological axons. The recognised production of reactive oxygen species particularly stemming from complex I and III, along with complex inhibition by nitric oxide and peroxynitrite, a result of chronic inflammation, points to the high vulnerability of mitochondria in MS.