Different in Situ Hybridization Patterns of Mitochondrial DNA in Cytochrome C Oxidase-deficient Extraocular Muscle Fibres in the Elderly

Overview

Journal Virchows Arch A Pathol Anat Histopathol

Specialty Anatomy & Histology

Date 1993 Jan 1

PMID 7679851

Citations 35

Authors

J Muller-Hocker

P Seibel

K Schneiderbanger

B KADENBACH

Affiliations

Soon will be listed here.

Abstract

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.

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References

Miquel J . An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cells. Arch Gerontol Geriatr. 1991; 12(2-3):99-117. DOI: 10.1016/0167-4943(91)90022-i. View

Anderson S, Bankier A, Barrell B, de Bruijn M, Coulson A, Drouin J . Sequence and organization of the human mitochondrial genome. Nature. 1981; 290(5806):457-65. DOI: 10.1038/290457a0. View

Enter C, Muller-Hocker J, Zierz S, Ruitenbeek W, Gerbitz K . Respiratory chain activity in tissues from patients (MELAS) with a point mutation of the mitochondrial genome [tRNA(Leu(UUR))]. FEBS Lett. 1991; 286(1-2):67-70. DOI: 10.1016/0014-5793(91)80942-v. View

Byrne E, Dennett X, Trounce I . Oxidative energy failure in post-mitotic cells: a major factor in senescence. Rev Neurol (Paris). 1991; 147(6-7):532-5. View

KADENBACH B, Muller-Hocker J . Mutations of mitochondrial DNA and human death. Naturwissenschaften. 1990; 77(5):221-5. DOI: 10.1007/BF01138485. View

Muller-Hocker J, Stunkel S, Pongratz D, Hubner G . Focal deficiency of cytochrome c oxidase and of mitochondrial ATPase with histochemical evidence of loosely coupled oxidative phosphorylation in a mitochondrial myopathy of a patient with bilateral ptosis. An enzyme histochemical, immunocytochemical.... J Neurol Sci. 1985; 69(1-2):27-36. DOI: 10.1016/0022-510x(85)90004-8. View

Muller-Hocker J, Seibel P, Schneiderbanger K, Zietz C, Gerbitz K, KADENBACH B . In situ hybridization of mitochondrial DNA in the heart of a patient with Kearns-Sayre syndrome and dilatative cardiomyopathy. Hum Pathol. 1992; 23(12):1431-7. DOI: 10.1016/0046-8177(92)90065-b. View

Byrne E, Dennett X, Trounce I, Henderson R . Partial cytochrome oxidase (aa3) deficiency in chronic progressive external ophthalmoplegia. Histochemical and biochemical studies. J Neurol Sci. 1985; 71(2-3):257-71. DOI: 10.1016/0022-510x(85)90064-4. View

Muller-Hocker J . Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: an age-related alteration. J Neurol Sci. 1990; 100(1-2):14-21. DOI: 10.1016/0022-510x(90)90006-9. View

10.

Yen T, Su J, King K, Wei Y . Ageing-associated 5 kb deletion in human liver mitochondrial DNA. Biochem Biophys Res Commun. 1991; 178(1):124-31. DOI: 10.1016/0006-291x(91)91788-e. View

11.

Ikebe S, Tanaka M, Ohno K, Sato W, Hattori K, Kondo T . Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence. Biochem Biophys Res Commun. 1990; 170(3):1044-8. DOI: 10.1016/0006-291x(90)90497-b. View

12.

Linnane A, Baumer A, Maxwell R, Preston H, Zhang C, Marzuki S . Mitochondrial gene mutation: the ageing process and degenerative diseases. Biochem Int. 1990; 22(6):1067-76. View

13.

Muller-Hocker J, Johannes A, Droste M, KADENBACH B, Pongratz D, Hubner G . Fatal mitochondrial cardiomyopathy in Kearns-Sayre syndrome with deficiency of cytochrome-c-oxidase in cardiac and skeletal muscle. An enzymehistochemical--ultra-immunocytochemical--fine structural study in longterm frozen autopsy tissue. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986; 52(4):353-67. DOI: 10.1007/BF02889977. View

14.

Muller-Hocker J, Nelson I, Lestienne P, Enter C, Riedele T, Gerbitz K . Different copy numbers of apparently identically deleted mitochondrial DNA in tissues from a patient with Kearns-Sayre syndrome detected by PCR. Biochem Biophys Res Commun. 1990; 169(3):1007-15. DOI: 10.1016/0006-291x(90)91994-4. View

15.

Shanske S, Moraes C, Lombes A, Miranda A, Bonilla E, Lewis P . Widespread tissue distribution of mitochondrial DNA deletions in Kearns-Sayre syndrome. Neurology. 1990; 40(1):24-8. DOI: 10.1212/wnl.40.1.24. View

16.

Arnaudo E, Dalakas M, Shanske S, Moraes C, DiMauro S, Schon E . Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet. 1991; 337(8740):508-10. DOI: 10.1016/0140-6736(91)91294-5. View

17.

Mita S, Schmidt B, Schon E, DiMauro S, Bonilla E . Detection of "deleted" mitochondrial genomes in cytochrome-c oxidase-deficient muscle fibers of a patient with Kearns-Sayre syndrome. Proc Natl Acad Sci U S A. 1989; 86(23):9509-13. PMC: 298526. DOI: 10.1073/pnas.86.23.9509. View

18.

Wallace D . Mitochondrial DNA mutations and neuromuscular disease. Trends Genet. 1989; 5(1):9-13. DOI: 10.1016/0168-9525(89)90005-x. View

19.

Goto Y, Nonaka I, Horai S . A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990; 348(6302):651-3. DOI: 10.1038/348651a0. View

20.

Morgan-Hughes J, Schapira A, Cooper J, Holt I, Harding A, Clark J . The molecular pathology of respiratory-chain dysfunction in human mitochondrial myopathies. Biochim Biophys Acta. 1990; 1018(2-3):217-22. DOI: 10.1016/0005-2728(90)90252-y. View