No conflicts of interest were declared.
Enhanced number and activity of mitochondria in multiple sclerosis lesions†
Article first published online: 26 MAY 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 219, Issue 2, pages 193–204, October 2009
How to Cite
Witte, M. E., Bø, L., Rodenburg, R. J., Belien, J. A., Musters, R., Hazes, T., Wintjes, L. T., Smeitink, J. A., Geurts, J. J., De Vries, H. E., van der Valk, P. and van Horssen, J. (2009), Enhanced number and activity of mitochondria in multiple sclerosis lesions. J. Pathol., 219: 193–204. doi: 10.1002/path.2582
- Issue published online: 10 SEP 2009
- Article first published online: 26 MAY 2009
- Accepted manuscript online: 26 MAY 2009 12:00AM EST
- Manuscript Accepted: 18 MAY 2009
- Manuscript Revised: 15 MAY 2009
- Manuscript Received: 24 MAR 2009
- Stichting Vrienden MS Research
- multiple sclerosis;
- oxidative stress
Mitochondrial dysfunction has been implicated in the development and progression of multiple sclerosis (MS) lesions. Mitochondrial alterations might occur as a response to demyelination and inflammation, since demyelination leads to an increased energy demand in axons and could thereby affect the number, distribution and activity of mitochondria. We have studied the expression of mitochondrial proteins and mitochondrial enzyme activity in active demyelinating and chronic inactive MS lesions. Mitochondrial protein expression and enzyme activity in active and chronic inactive MS lesions was investigated using (immuno)histochemical and biochemical techniques. The number of mitochondria and their co-localization with axons and astrocytes within MS lesions and adjacent normal-appearing white matter (NAWM) was quantitatively assessed. In both active and inactive lesions we observed an increase in mitochondrial protein expression as well as a significant increase in the number of mitochondria. Mitochondrial density in axons and astrocytes was significantly enhanced in active lesions compared to adjacent NAWM, whereas a trend was observed in inactive lesions. Complex IV activity was strikingly up-regulated in MS lesions compared to control white matter and, to a lesser extent, NAWM. Finally, we demonstrated increased immunoreactivity of the mitochondrial stress protein mtHSP70 in MS lesions, particularly in astrocytes and axons. Our data indicate the occurrence of severe mitochondrial alterations in MS lesions, which coincides with enhanced mitochondrial oxidative stress. Together, these findings support a mechanism whereby enhanced density of mitochondria in MS lesions might contribute to the formation of free radicals and subsequent tissue damage. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.