Electron transfer complexes I and IV of platelets are abnormal in Parkinson's disease but normal in Parkinson-plus syndromes
Abstract
Using a technique which requires only 100 ml blood we investigated the electron transfer complexes (ETC) I, III and IV in platelet mitochondria of 44 control subjects, 27 patients with idiopathic Parkinson's disease and eight patients with Parkinson-plus syndromes due to multiple system atrophy. In both control subjects and patients, ETC measurements were repeated at intervals of several months. The activities varied considerably among normal subjects, but intra-individual variation of ETC activities were low at repetitive measurements. In normal subjects there was no correlation between enzyme activities and age or training state. There was no difference in enzyme activities between smokers and non-smokers in the control group. Complex I activity was lower in Parkinson's disease patients than in controls (14 versus 29 nmol/min/mg platelet protein; P < 0.001). Furthermore, the group difference in complex IV activity also reached statistical significance (83 versus 58 nmol/min/mg platelet protein; P < 0.001). Additionally, in some Parkinson's disease patients, activities of complex III were low and lay outside the control range, but the group difference did not reach significance. There was no correlation between complex I activity and disease duration or severity as well as the daily L-dopa dose in Parkinson's disease patients. Repeated measurements in five Parkinson's disease patients in the earliest stages of their illness demonstrated that the decrease in complex I and IV activities can develop rapidly within 1 year. In Parkinson-plus patients suffering from multiple system atrophy the ETC activities were normal.
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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 [13]
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“The role of mitochondrial dysfunction in the pathogenesis of PD is also supported by the fact that the dopaminergic toxin MPTP inhibits complex I (Benecke et al., 1993) and the complex I inhibitor rotenone can reproduce neuropathological features of PD (Schapira, 1994).”
BackgroundInfluentialMitochondrial DNA polymorphisms in pathologically proven Parkinson’s disease
Bandmann, O., Sweeney, M. G., Daniel, S. E., MARSDEN, C. D., & Wood, N. W. (1997) · Journal of Neurology · doi:10.1007/s004150050082 · Cited by 53 · see citing works
Mutations in Mitochondrial Complex III Uniquely Affect Complex I in Caenorhabditis elegans
Suthammarak, W., Morgan, P. G., & Sedensky, M. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159608 · Cited by 54 · see citing works
Astrocytes Attenuate Mitochondrial Dysfunctions in Human Dopaminergic Neurons Derived from iPSC
Du, F., Yu, Q., Chen, A., Chen, D., & Yan, S. S. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.12.021 · Cited by 54 · see citing works
“In addition, combined decreased complex I and IV activity was seen in the platelet mitochondria of PD (Benecke et al., 1993) and 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-induced animal models of PD (Desai et al.”
BackgroundOxidative stress in skin fibroblasts cultures from patients with Parkinson's disease
del Hoyo, P., García‐Redondo, A., Bustos, F., Molina, J. A., Sayed, Y., Alonso‐Navarro, H., Caballero, L., Arenas, J., Agúndez, J. A. G., & Jiménez‐Jiménez, F. J. (2010) · BMC Neurology · doi:10.1186/1471-2377-10-95 · Cited by 50 · see citing works
“There have been reported normal activities [6,18-20], or decreased activities of complex I [21-26], complex II+III [25] or complex IV [24].”
BackgroundReduced platelet glutamate uptake in Parkinson's disease
Ferrarese, C., Zoia, C., Pecora, N., Piolti, R., Frigo, M., Bianchi, G., Sala, G., Begni, B., Riva, R., & Frattola, L. (1999) · Journal of Neural Transmission · doi:10.1007/s007020050189 · Cited by 51 · see citing works
“However, defects in complex-1 mitochondrial enzymes, which make dopaminergic cells more sensitive to oxidative stress, have been found not only in substantia nigra of PD patients (Hattori et al., 1991), but also in peripheral tissues (Shoffner et al., 1991) and in blood platelets ( Benecke et al., 1993; Krige et al.,…”
BackgroundResultMitochondrial DNA–Related Mitochondrial Dysfunction in Neurodegenerative Diseases
Swerdlow, R. H. (2002) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2002-126-0271-mdrmdi · Cited by 50 · see citing works
Subrahmanian, N., & LaVoie, M. J. (2021) · Brain Research · doi:10.1016/j.brainres.2021.147434 · Cited by 48 · see citing works
“Five studies from four different research groups considering samples from 98 PD patients observed a 16–51% decrease in isolated CI activity or combined with CII and CIV deficiency, with no significant correlation between CI deficiency and age at onset, duration of disease, or severity of disease (Benecke et al., 1993;…”
BackgroundResultInfluentialA Complex Genome-MicroRNA Interplay in Human Mitochondria
Shinde, S., & Bhadra, U. (2015) · BioMed Research International · doi:10.1155/2015/206382 · Cited by 49 · see citing works
In vivo vulnerability of dopamine neurons to inhibition of energy metabolism
Zeevalk, G. D., Manzino, L., Hoppe, J., & Sonsalla, P. K. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00892-8 · Cited by 49 · see citing works
Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness
Cieri, D., Brini, M., & Calí, T. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.153 · Cited by 47 · see citing works
Peripheral markers of oxidative stress in Parkinson’s disease. the role of L-DOPA
Martignoni, E., Blandini, F., Godi, L., Desideri, S., Pacchetti, C., Mancini, F., & Nappi, G. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00075-1 · Cited by 47 · see citing works
Assessment of Platelet Respiration as Emerging Biomarker of Disease
Petruş, A., Lighezan, D. L., Dănilă, M. D., Duicu, O., Sturza, A., Muntean, D. M., & Ioniță, I. (2019) · Physiological Research · doi:10.33549/physiolres.934032 · Cited by 45 · see citing works
“Ageing Decreased stability of CI Decreased energy conservation Decreased CIV activity (D'Aurelio et al. 2001) Asthma Astmatic patients present increased oxygen utilization and efficients usage of substrates in platelets as previously shown in the airways (Weiling Xu 2015) Pulmonary hypertension - Increased mitochondri…”
BackgroundInfluentialMITOCHONDRIAL COMPLEX I, II/III, AND IV ACTIVITIES IN FAMILIAL AND SPORADIC PARKINSON'S DISEASE
Hanagasi, H. A., AYRIBAS, D., Baysal, K., & Emre, M. (2005) · International Journal of Neuroscience · doi:10.1080/00207450590523017 · Cited by 45 · see citing works
“…mitochondria, the severity of the complex I defect in PD varies from 16 to 71% in published studies (Parker et al., 1989; Yoshino et al., 1992; Benecke et al., 1993; Krige et al., 1993; Haas et al., 1995); some groups have reported normal complex I activity in platelets (Bravi et al., 1992;…”
BackgroundInfluentialGenetic aspects of Parkinson's disease
Bandmann, O., MARSDEN, C. D., & Wood, N. W. (1998) · Movement Disorders · doi:10.1002/mds.870130203 · Cited by 47 · see citing works
Quantitative study of mitochondrial complex I in platelets of parkinsonian patients
Blandini, F., Nappi, G., & Timothy Greenamyre, J. (1998) · Movement Disorders · doi:10.1002/mds.870130106 · Cited by 44 · see citing works
Early-onset Parkinson disease caused by a mutation in CHCHD2 and mitochondrial dysfunction
Lee, R. G., Sedghi, M., Salari, M., et al. (2018) · Neurology Genetics · doi:10.1212/nxg.0000000000000276 · Cited by 44 · see citing works
“Although reduced complex IV activity has been previously reported in PD, there is much less evidence for impaired complex IV activity, contributing to PDdevelopment.(27) The reduction in complex IV formation is consistent with studies finding an interaction between CHCHD2 and the cytochrome c–binding protein MICS1.”
BackgroundMitochondrial dysfunction and possible treatments in Parkinson's disease—a review
Shults, C. W. (2004) · Mitochondrion · doi:10.1016/j.mito.2004.07.028 · Cited by 44 · see citing works
Kim, C. B. Y., Pier, L. P., & Spear, P. D. (1997) · The Anatomical Record · doi:10.1002/(sici)1097-0185(199701)247:1 · Cited by 42 · see citing works
Swerdlow, R. H., Parks, J. K., Cassarino, D. S., Binder, D. R., Bennett, J. P., Iorio, G. D., Golbe, L. I., & Parker, W. D. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7674 · Cited by 43 · 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
“Furthermore decreased enzyme activities were reported in muscle, fibroblasts and platelets (Benecke et al., 1993; Haas et al., 1995; Krige et al., 1992; Wiedemann et al., 1999).”
- Authors
- Benecke, R., Strumper, P., & Weiss, H.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Benecke, R.
- ORCID
- Benecke, R.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 1993-12-01
- Volume
- 116
- Issue
- 6
- Pages
- 1451-1463
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2005045122
- Cited by
- 220
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 1 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- Parkinson's disease, atypical parkinsonism, multiple system atrophy, electron transfer complex, complex I, cytochrome bc1 complex, cytochrome c oxidase, platelet mitochondria, mitochondrial enzyme activity, disease duration
- MeSH terms
- Aged, Aged, 80 and over, Blood Platelets, Electron Transport Complex IV, Electron Transport, Humans, Middle Aged, Mitochondria, Parkinson Disease, Parkinson Disease, Secondary, Syndrome, Electron Transport Complex III, NAD(P)H Dehydrogenase (Quinone)
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