Virchows Archiv A

, Volume 422, Issue 1, pp 7–15

Different in situ hybridization patterns of mitochondrial DNA in cytochrome c oxidase-deficient extraocular muscle fibres in the elderly

Authors

  • J. Müller-Höcker
    • Pathologisches Institut der Universität München
  • P. Seibel
    • Institute of BiochemistryMarburg University
  • K. Schneiderbanger
    • Pathologisches Institut der Universität München
  • B. Kadenbach
    • Institute of BiochemistryMarburg University
Original Articles

DOI: 10.1007/BF01605127

Cite this article as:
Müller-Höcker, J., Seibel, P., Schneiderbanger, K. et al. Vichows Archiv A Pathol Anat (1993) 422: 7. doi:10.1007/BF01605127
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Summary

Previous studies have revealed an increase of cytochrome c oxidase-deficient fibres/cells in the skeletal and heart muscle of humans during ageing. The enzyme defect is due to a lack of both mitochondrial and nuclear coded enzyme subunits. In the present investigation in situ hybridization of mitochondrial DNA (mtDNA) has been performed on extraocular muscles of humans over 70 years of age to show whether mutated mtDNA with the so called common deletion of 4,977 basepairs at position 8,482–13,460 of mtDNA accumulates in the cytochrome c oxidase-deficient fibres. The cytochrome c oxidase-deficient fibres revealed different hybridization patterns: a normal hybridization signal with three different mtDNA probes, a reduced or lacking signal with all three probes indicating depletion of mtDNA and a selective hybridization defect with the probe recognizing the “common deletion” region of mtDNA as evidence of mtDNA deletion. The results suggest that during ageing defects of cytochrome c oxidase are associated with different molecular alterations of mtDNA. Deletion and depletion of mtDNA are not the only nor probably the leading mechanisms responsible for the loss of respiratory chain capacity during ageing. The normal hybridization signal in most of the cytochrome c oxidase-deficient fibres and the loss of mitochondrial and nuclear protein subunits indicate the involvement of other, especially nuclear factors.

Key words

Mitochondrial DNAAgeingCytochrome c oxidase deficiencyExtraocular muscles

Copyright information

© Springer-Verlag 1993