Astrocytic Changes in Mitochondrial Oxidative Phosphorylation Protein Levels in Parkinson's Disease
Open accessAbstract
Background: Mitochondrial dysfunction within neurons, particularly those of the substantia nigra, has been well characterized in Parkinson's disease and is considered to be related to the pathogenesis of this disorder. Dysfunction within this important organelle has been suggested to impair neuronal communication and survival; however, the reliance of astrocytes on mitochondria and the impact of their dysfunction on this essential cell type are less well characterized. Objective: This study aimed to uncover whether astrocytes harbor oxidative phosphorylation (OXPHOS) deficiencies in Parkinson's disease and whether these deficiencies are more likely to occur in astrocytes closely associated with neurons or those more distant from them. Methods: Postmortem human brain sections from patients with Parkinson's disease were subjected to imaging mass cytometry for individual astrocyte analysis of key OXPHOS proteins across all five complexes. Results: We show the variability in the astrocytic expression of mitochondrial proteins between individuals. In addition, we found that there is evidence of deficiencies in respiratory chain subunit expression within these important glia and changes, particularly in mitochondrial mass, associated with Parkinson's disease and that are not simply a consequence of advancing age. Conclusion: Our data show that astrocytes, like neurons, are susceptible to mitochondrial defects and that these could have an impact on their reactivity and ability to support neurons in Parkinson's disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Compromised function in astrocytic mitochondria could have profound detrimental effects on neuronal function within the substantia nigra pars compacta, corroborated by evidence that SNc astrocytes demonstrate deficiencies in mitochondrial oxidative phosphorylation protein complex expression in postmortem samples of patients with clinically diagnosed Parkinson's disease.
“Compromised function in astrocytic mitochondria could have profound detrimental effects on neuronal function within the SNc”
From Mitochondrial DNA Damage in Substantia Nigra Pars Compacta Astrocytes Exacerbates Dopaminergic Neuron Loss in a 6-Hydroxydopamine Mouse Model of Parkinsonism (2026) · cites this paper as Chen et al. 2022
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
Bélanger, M., Allaman, I., & Magistretti, P. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.016 · Cited by 2,313 · see citing works
Transcellular degradation of axonal mitochondria
Davis, C.-H. O., Kim, K.-Y., Bushong, E. A., Mills, E. A., Boassa, D., Shih, T., Kinebuchi, M., Phan, S., Zhou, Y., Bihlmeyer, N. A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404651111 · Cited by 673 · see citing works
Elusive roles for reactive astrocytes in neurodegenerative diseases
Ben Haim, L., Carrillo-de Sauvage, M.-A., Ceyzériat, K., & Escartin, C. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00278 · Cited by 453 · see citing works
Flagged first, then by citations
Research works printed but not linked: 32
- Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. Mitochondrial complex I deficiency in Parkinson's disease. Lancet 1989;1(8649):1269.
- Langston JW, Ballard PA Jr. Parkinson's disease in a chemist working with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. N Engl J Med 1983;309(5):310.
- Kam TI, Hinkle JT, Dawson TM, Dawson VL. Microglia and astrocyte dysfunction in Parkinson's disease. Neurobiol Dis 2020;144:105028.
- Booth HDE, Hirst WD, Wade-Martins R. The role of astrocyte dysfunction in Parkinson's disease pathogenesis. Trends Neurosci 2017;40(6):358-370.
- Fossati G, Matteoli M, Menna E. Astrocytic factors controlling synaptogenesis: a team play. Cell 2020;9(10):2173-2193.
- Fullana N, Gasull-Camos J, Tarres-Gatius M, Castane A, Bortolozzi A, Artigas F. Astrocyte control of glutamatergic activity: downstream effects on serotonergic function and emotional behav- ior. Neuropharmacology 2020;166:107914.
- Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol 2010;119(1):7-35.
- Joe EH, Choi DJ, An J, Eun JH, Jou I, Park S. Astrocytes, microglia, and Parkinson's disease. Exp Neurobiol 2018;27(2):77-87.
- He Y, Appel S, Le W. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res 2001;909(1-2):187-193.
- Hu X, Zhang D, Pang H, et al. Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. J Immunol 2008;181(10):7194-7204.
- Chen C, Turnbull DM, Reeve AK. Mitochondrial dysfunction in Parkinson's disease-cause or consequence? Biology 2019;8(2):38.
- Chen C, McDonald D, Blain A, et al. Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson's disease. NPJ Parkinsons Dis 2021;7(1):39.
- Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 2006;38(5):518-520.
- Bender A, Krishnan KJ, Morris CM, et al. High levels of mitochon- drial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 2006;38(5):515-517.
- Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK. Mitochondrial import and accumula- tion of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem 2008; 283(14):9089-9100.
- Ludtmann MHR, Angelova PR, Horrocks MH, et al. α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson's disease. Nat Commun 2018;9(1):2293.
- McAvoy K, Kawamata H. Glial mitochondrial function and dysfunction in health and neurodegeneration. Mol Cell Neurosci 2019;101:103417.
- Bolaños JP. Bioenergetics and redox adaptations of astrocytes to neuronal activity. J Neurochem 2016;139:115-125.
- Proia P, Di Liegro CM, Schiera G, Fricano A, Di Liegro I. Lactate as a metabolite and a regulator in the central nervous system. Int J Mol Sci 2016;17(9):1450.
- Russell OM, Gorman GS, Lightowlers RN, Turnbull DM. Mitochondrial diseases: hope for the future. Cell 2020;181(1): 168-188.
- Fiebig C, Keiner S, Ebert B, et al. Mitochondrial dysfunction in astrocytes impairs the generation of reactive astrocytes and enhances neuronal cell death in the cortex upon photothrombotic lesion. Front Mol Neurosci 2019;12:40.
- Chang Q, Ornatsky O, Hedley D. Staining of frozen and formalin- fixed, paraffin-embedded tissues with metal-labeled antibodies for imaging mass cytometry analysis. Curr Protoc Cytom 2017;82: 12.47.11-12.47.18.
- Warren C, McDonald D, Capaldi R, et al. Decoding mitochondrial heterogeneity in single muscle fibres by imaging mass cytometry. Sci Rep 2020;10(1):15336.
- Bankhead P, Loughrey MB, Fernandez JA, et al. QuPath: open source software for digital pathology image analysis. Sci Rep 2017; 7(1):16878.
- Rocha MC, Grady JP, Grunewald A, et al. A novel immunofluores- cent assay to investigate oxidative phosphorylation deficiency in mitochondrial myopathy: understanding mechanisms and improving diagnosis. Sci Rep 2015;5:15037.
- Oberg AL, Mahoney DW. Linear mixed effects models. Methods Mol Biol 2007;404:213-234.
- James G, Witten D, Hastie T, Tibshirani R. An Introduction to Sta- tistical Learning. New York, USA: Springer; 2013.
- Kruschke JK. Bayesian estimation supersedes the t test. J Exp Psychol Gen 2013;142(2):573-603.
- Surmeier DJ, Obeso JA, Halliday GM. Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 2017;18(2): 101-113.
- Bantle CM, Hirst WD, Weihofen A, Shlevkov E. Mitochondrial dys- function in astrocytes: a role in Parkinson's disease? Front Cell Dev Biol 2021;8:608026.
- Lovatt D, Sonnewald U, Waagepetersen HS, et al. The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 2007;27(45):12255-12266.
- Hayakawa K, Esposito E, Wang X, et al. Transfer of mitochondria from astrocytes to neurons after stroke. Nature 2016;535(7613): 551-555.
Cited by
Sorted by citations
Walecha, V., & Luthra, P. M. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04559-9 · Cited by 12 · see citing works
Ayala, D. A., Hall, G. M., Das, D., Tijerina, E., Villagran, L. L., Khan, Z., Paliwal, D., Anand, A., Rimer, M., & Srinivasan, R. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01713-x · Cited by 1 · see citing works
- Authors
- Chen, C., Mossman, E., Malko, P., McDonald, D., Blain, A. P., Bone, L., Erskine, D., Filby, A., Vincent, A. E., Hudson, G., & Reeve, A. K.
- Affiliations
- Wellcome Centre for Mitochondrial Research (GB)
- University of Leeds (GB)
- Newcastle University (GB)
- Corresponding author
- Reeve, Amy K.
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2021-11-15
- Volume
- 37
- Issue
- 2
- Pages
- 302-314
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W3212623032
- Cited by
- 36
- References
- 3
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 3
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Movement Disorders (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Parkinson's UK (F‐1401)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, astrocytes, mitochondrial dysfunction, oxidative phosphorylation, respiratory chain complexes, mitochondrial proteins, substantia nigra, astrocyte-neuron interaction, imaging mass cytometry, postmortem brain
- MeSH terms
- Astrocytes, Humans, Oxidative Phosphorylation, Parkinson Disease, Substantia Nigra, Mitochondrial Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
