Re-evaluation of the dysfunction of mitochondrial respiratory chain in skeletal muscle of patients with Parkinson?s disease
Abstract
The origin and tissue distribution of the mitochondrial dysfunction in Parkinson's disease (PD) remains still a matter of controversy. To re-evaluate a probably free radical-born, generalized mitochondrial impairment in PD, we applied optimized enzymatic assays, high resolution oxygraphic measurements of permeabilized muscle fibers, and application of metabolic control analysis to skeletal muscle samples of 19 PD patients and 36 age-matched controls. We detected decreased activities of respiratory chain complexes I and IV being accompanied by increased flux control coefficients of complexes I and IV on oxygen consumption of muscle fibers. We further investigated if randomly distributed point mutations in two discrete regions of the mitochondrial DNA are increased in PD muscle, and if they could contribute to the mitochondrial impairment. Our data confirm the previously debated presence of a mild mitochondrial defect in skeletal muscle of patients with PD which is accompanied with an about 1.5 to 2-fold increase of point mutated mtDNA.
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Impairment of mitochondrial complex-I activity has been observed in the substantia nigra, platelets, and skeletal muscle of PD patients, in some but not all studies.
“An impairment of mitochondrial complex-I activity has been observed in the substantia nigra (SN), platelets, and skeletal muscle of PD patients 1, 9-13, in some but not in all studies14, 15.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [12]
Cites
Sequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,640 · see citing works
Oxidative stress in Parkinson's disease
Jenner, P. (2003) · Annals of Neurology · doi:10.1002/ana.10483 · Cited by 2,053 · see citing works
MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE
Schapira, A. H. V., Cooper, J. A. D., Dexter, D. T., Jenner, P. G., Clark, J. B., & MARSDEN, C. D. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92366-0 · Cited by 1,757 · see citing works
[45] Cytochrome oxidase from beef heart mitochondria
Wharton, D. C., & Tzagoloff, A. (1967) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(67)10048-7 · Cited by 1,266 · see citing works
A new mitochondrial disease associated with mitochondrial DNA heteroplasmy.
Holt, I. J., Harding, A. E., Petty, R., & MORGAN-HUGHES, J. A. (1990) · PubMed · Cited by 996 · see citing works
Trounce, I. A., Kim, Y. L., Jun, A. S., & Wallace, D. C. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)64044-0 · Cited by 749 · see citing works
Deficiencies in Complex I subunits of the respiratory chain in Parkinson's disease
Mizuno, Y., Ohta, S., Tanaka, M., Takamiya, S., Suzuki, K., SATO, T. A., Oya, H., Ozawa, T., & Kagawa, Y. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91141-8 · Cited by 735 · see citing works
Helbock, H. J., Beckman, K. B., Shigenaga, M. K., Walter, P. B., Woodall, A., Yeo, H. C. H., & Ames, B. N. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.288 · Cited by 688 · see citing works
Mitochondrial Polymorphisms Significantly Reduce the Risk of Parkinson Disease
van der Walt, J. M., Nicodemus, K. K., Martin, E. R., Scott, W. K., NANCE, M. A., Watts, R. L., Hubble, J. P., Haines, J. L., Koller, W. C., Lyons, K. E., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/373937 · Cited by 537 · see citing works
Mitochondrial DNA Variants Observed in Alzheimer Disease and Parkinson Disease Patients
Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. F., Mirra, S. S., Beal, M. F., Yang, C.-C., Gearing, M., Salvo, R., et al. (1993) · Genomics · doi:10.1006/geno.1993.1299 · Cited by 450 · see citing works
Permeabilized cell and skinned fiber techniques in studies of mitochondrial function in vivo
Saks, V. A., Veksler, V., Kuznetsov, A. V., Kay, L., Sikk, P., Tiivel, T., Tranqui, L., Olivares, J., Winkler, K., Wiedemann, F. R., et al. (1998) · Springer eBooks · doi:10.1007/978-1-4615-5653-4_7 · Cited by 361 · see citing works
Self-citationMitochondrial DNA and respiratory chain function in spinal cords of ALS patients
Wiedemann, F. R., Manfredi, G., Mawrin, C., Beal, M. F., & Schon, E. A. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00731.x · Cited by 360 · see citing works
Self-citationBRAIN, SKELETAL MUSCLE AND PLATELET HOMOGENATE MITOCHONDRIAL FUNCTION IN PARKINSON'S DISEASE
MANN, V. M., COOPER, J. M., KRIGE, D., DANIEL, S. E., SCHAPIRA, A. H. V., & MARSDEN, C. D. (1992) · Brain · doi:10.1093/brain/115.2.333 · Cited by 346 · cited 1× · see citing works
“Bindoff et al. (1989, 1991) þþ þ Shoffner et al. (1991) þþ þ Nakagawa-Hattori et al. (1992) þ� � Mann et al. (1992) �� � Anderson et al. (1993) �� � Cardellach et al. (1993) þ� þ Di Monte et al. (1993) �� � DiDonato et al. (1993) �� � Blin et al. (1994) þ� þ Reichmann et al. (1994) �� � Taylor et al. (1994) �� � Wiede…”
Mitochondrial oxidative phosphorylation defects in parkinson's disease
Shoffner, J. M., Watts, R. L., Juncos, J. L., Torroni, A., & Wallace, D. C. (1991) · Annals of Neurology · doi:10.1002/ana.410300304 · Cited by 333 · see citing works
Mitochondria and degenerative disorders
Orth, M., & Schapira, A. H. V. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1425 · Cited by 278 · see citing works
Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in parkinson's disease
Hattori, N., Tanaka, M., Ozawa, T., & Mizuno, Y. (1991) · Annals of Neurology · doi:10.1002/ana.410300409 · Cited by 275 · see citing works
A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness
Reid, F. M., Vernham, G. A., & Jacobs, H. T. (1994) · Human Mutation · doi:10.1002/humu.1380030311 · Cited by 266 · see citing works
Wiedemann, F. R., Winkler, K., Kuznetsov, A. V., Bartels, C., Vielhaber, S., Feistner, H., & Kunz, W. S. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00008-2 · Cited by 262 · see citing works
Self-citationMITOCHONDRIAL FUNCTION IN PARKINSON'S DISEASE
Bindoff, L. A., Birch‐Machin, M. A., Cartlidge, N. E. F., Parker, W. D., & Turnbull, D. M. (1989) · The Lancet · doi:10.1016/s0140-6736(89)90291-2 · Cited by 245 · see citing works
Heinrich, R., & Rapoport, T. A. (1974) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1974.tb03319.x · Cited by 241 · see citing works
Respiratory chain abnormalities in skeletal muscle from patients with Parkinson's disease
Bindoff, L. A., Birch‐Machin, M. A., Cartlidge, N. E. F., Parker, W. D., & Turnbull, D. M. (1991) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(91)90311-t · Cited by 229 · see citing works
Mitochondrial DNA repair of oxidative damage in mammalian cells
Bohr, V. A., Stevnsner, T., & de Souza-Pinto, N. C. (2002) · Gene · doi:10.1016/s0378-1119(01)00813-7 · Cited by 204 · see citing works
[43]Cytochemistry and immunocytochemistry of mitochondria in tissue sections
Sciacco, M., & Bonilla, E. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)64045-2 · Cited by 192 · see citing works
Mitochondrial involvement in Parkinson's disease
Orth, M. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(01)00124-3 · Cited by 188 · see citing works
Mismatch repair activity in mammalian mitochondria
Mason, P. A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg167 · Cited by 185 · see citing works
Blin, O. J., Desnuelle, C., Rascol, O., Borg, M., Paul, H. P. S., Azulay, J., Billé, F., Figarella-Branger, D. F., Coulom, F., Pellissier, J., et al. (1994) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(94)90248-8 · Cited by 182 · see citing works
Age‐dependent decline of DNA repair activity for oxidative lesions in rat brain mitochondria
Chen, D., Cao, G., Hastings, T. G., Feng, Y., Pei, W., O'Horo, C., & Chen, J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00916.x · Cited by 139 · see citing works
Zhang, C., Linnane, A. W., & Nagley, P. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2158 · Cited by 134 · see citing works
Mitochondria1 respiratory chain activity in skeletal muscle from patients with Parkinson's disease
Cardellach, F., Martí, M. J., Fernández‐Solà, J., Marín, C., Hoek, J. B., TOLOSA, E. S., & Urbano-Márquez, A. (1993) · Neurology · doi:10.1212/wnl.43.11.2258 · Cited by 131 · see citing works
Free radicals in Parkinson's disease
Koutsilieri, E., Scheller, C., Grünblatt, E., Keinosuke, N. A. R. A., Li, J., & Riederer, P. F. (2002) · Journal of Neurology · doi:10.1007/s00415-002-1201-7 · Cited by 117 · see citing works
Base excision repair capacity in mitochondria and nuclei: tissue‐specific variations
Karahalıl, B., Hogue, B. A., de Souza-Pinto, N. C., et al. (2002) · The FASEB Journal · doi:10.1096/fj.02-0463com · Cited by 114 · see citing works
Respiratory chain and mitochondrial DNA in muscle and brain in Parkinson's disease patients
DiDonato, S., Zeviani, M., Giovannini, P., Savarese, N., Rimoldi, M., Mariotti, C., Girotti, F., & CARACENI, T. (1993) · Neurology · doi:10.1212/wnl.43.11.2262 · Cited by 98 · see citing works
Pallotti, F., Chen, X., Bonilla, E., & Schon, E. A. (1996) · PubMed Central · Cited by 93 · see citing works
Functional Imaging of Mitochondria in Saponin-permeabilized Mice Muscle Fibers
Kuznetsov, A. V., Mayboroda, O. A., Kunz, D., Winkler, K., SCHUBERT, W. J., & Kunz, W. S. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.5.1091 · Cited by 88 · see citing works
Self-citationMiró, Ò., Cardellach, F., Barrientos, A., Casademont, J., Rötig, A., & Rustin, P. (1998) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(97)00204-5 · Cited by 78 · see citing works
Is Parkinson's disease a mitochondrial disorder?
Nakagawa-Hattori, Y., Yoshino, H., Kondo, T., Mizuno, Y., & Horai, S. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90205-y · Cited by 71 · see citing works
Sperl, W., Skladal, D., Gnaiger, E., et al. (1997) · Springer eBooks · doi:10.1007/978-1-4615-6111-8_11 · Cited by 70 · see citing works
Wiedemann, F. R., Vielhaber, S., Schröder, R., Elger, C. E., & Kunz, W. S. (2000) · Analytical Biochemistry · doi:10.1006/abio.1999.4434 · Cited by 65 · see citing works
Self-citationTaylor, D. J., Krige, D., Barnes, P. R. J., Kemp, G. J., Carroll, M. T., Mann, V. M., Cooper, J. A. D., MARSDEN, C. D., & Schapira, A. H. V. (1994) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(94)90245-3 · Cited by 64 · see citing works
Kuznetsov, A. V., Winkler, K., Kirches, E., Lins, H., Feistner, H., & Kunz, W. S. (1997) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(96)00072-5 · Cited by 62 · see citing works
Self-citationNitric oxide-induced damage to mtDNA and its subsequent repair
Grishko, V. I., Druzhyna, N., LeDoux, S. P., et al. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.22.4510 · Cited by 55 · see citing works
Novel mitochondrial DNA mutations in Parkinson's disease
Richter, G., Sonnenschein, A., Grünewald, T. G. P., Reichmann, H., & Janetzky, B. (2002) · Journal of Neural Transmission · doi:10.1007/s007020200060 · Cited by 42 · see citing works
Deficiencies of NADH and succinate dehydrogenases in degenerative diseases and myopathies
Singer, T. P., Ramsay, R. R., & Ackrell, B. A. C. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(95)00030-8 · Cited by 39 · see citing works
No evidence for altered muscle mitochondrial function in Parkinson's disease.
Anderson, J. J., Bravi, D., Ferrari, R., Davis, T. L., Baronti, F., Chase, T. N., & Dagani, F. (1993) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.56.5.477 · Cited by 39 · see citing works
Isoforms of human cytochrome‐c oxidase
Kuilenburg, A. B. P., Dekker, H. L., den Bogert, C. V., NIEBOER, P., GELDER, B. F. V., & Muijsers, A. O. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16162.x · Cited by 35 · see citing works
Wiedemann, F. R., Winkler, K., Lins, H., Wallesch, C., & Kunz, W. S. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07870.x · Cited by 25 · see citing works
Self-citationReichmann, H., Janetzky, B., Bischof, F., et al. (2008) · European Neurology · doi:10.1159/000117053 · Cited by 25 · see citing works
Does mitochondrial respiratory chain dysfunction have a role in common neurodegenerative disorders?
Byrne, E. (2002) · Journal of Clinical Neuroscience · doi:10.1054/jocn.2001.0991 · Cited by 24 · see citing works
Saxowsky, T. T., Matsumoto, Y., & Englund, P. T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206654200 · Cited by 16 · see citing works
Kirches, E., Winkler, K., Warich-Kirches, M., et al. (1998) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005306725644 · Cited by 10 · see citing works
Self-citationIs there mitochondrial dysfunction in amyotrophic lateral sclerosis skeletal muscle?
Vielhaber, S., Kudin, A. P., Winkler, K., Wiedemann, F. R., Schröder, R., Feistner, H., Heinze, H., Elger, C. E., & Kunz, W. S. (2003) · Annals of Neurology · doi:10.1002/ana.10564 · Cited by 8 · see citing works
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Chaturvedi, R. K., & Beal, M. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.027 · Cited by 294 · see citing works
Loss of <i>Parkin</i> impairs mitochondrial function and leads to muscle atrophy
Peker, N., Donipadi, V., Sharma, M., McFarlane, C., & Kambadur, R. (2018) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00064.2017 · Cited by 68 · see citing works
- Authors
- Winkler-Stuck, K., Kirches, E., Mawrin, C., Dietzmann, K., Lins, H., Wallesch, C.-W., Kunz, W. S., & Wiedemann, F. R.
- Affiliations
- Otto-von-Guericke-Universität Magdeburg (DE)
- University of Bonn (DE)
- Venue
- Journal of Neural Transmission
- Published
- 2004-08-03
- Volume
- 112
- Issue
- 4
- Pages
- 499-518
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W2020699733
- Cited by
- 63
- References
- 51
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 4 · 2014: 5
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Deutsche Parkinson Vereinigung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- Parkinson's disease, mitochondrial dysfunction, electron transport chain, skeletal muscle, complex I, cytochrome c oxidase, flux control coefficients, oxygen consumption, mitochondrial DNA point mutations, free radicals, metabolic control analysis
- MeSH terms
- Adult, Aged, DNA Mutational Analysis, DNA, Mitochondrial, Electron Transport, Female, Free Radicals, Humans, Male, Middle Aged, Mitochondria, Oxidative Phosphorylation, Parkinson Disease, Point Mutation, Oxidative Stress, Muscle, Skeletal, Cell Respiration, Mitochondrial Diseases
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