Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethical Statement
2.2. Study Cohort for Subsequent Proteomic Analyses
2.3. Tissue and Sample Preparation for LC-MS/MS Experiments
2.4. Electron Microscopy
2.5. Mass Spectrometric Analysis
2.6. Data Analysis
2.7. Analysis of Protein Annotations
2.8. Western Blotting
3. Results
3.1. Western Blot Analysis Identifies a Sub-Fraction Suitable for In-Depth Proteomic Analysis
3.2. Core Proteome of Synapses Isolated from the Substantia Nigra
3.3. Functional Annotation of the Core Proteome
3.4. Proteins Altered between Parkinson’s Disease Patients and Control Subjects
3.5. Confirmation of Altered Mitochondrial Translation in PD Synaptosomes
4. Discussion
4.1. Isolation of Synaptosomes from and Definition of Synaptosome Core Proteome in the Substantia Nigra
4.2. Identification of PD-Related Changes
4.3. Changed Mitochondrial Translation and mtDNA Synthesis in PD
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Group | Gender | Age (in years) | Ø Age ± SD | DS | PMI (h) | Ø PMI (h) ± SD | Tissue Weight (g) | PD Braak/ AD Braak | CDR | CERAD |
---|---|---|---|---|---|---|---|---|---|---|
Control | Female | 88 | 78.8 ± 6.9 | NA | ~13:00 | 14:04 ± 0.13 | 0.2306 | NA | NA | NA |
Male | 80 | NA | 19:39 | 0.4616 | NA | NA | NA | |||
Female | 73 | NA | 13:30 | 0.4076 | NA | NA | NA | |||
Male | 82 | NA | 12:11 | 0.2530 | NA | NA | NA | |||
Female | 71 | NA | 12:00 | 0.3925 | NA | NA | NA | |||
PD | Female | 87 | 80.8 ± 6.8 | 3 | 13:08 | 14:19 ± 0.12 | 0.2461 | 3/3 | 0 | none |
Male | 88 | 5 | 11:20 | 0.3607 | 5/3 | 0.5 | moderate | |||
Female | 75 | 3 | 14:40 | 0.6556 | 3/2 | 0 | moderate | |||
Male | 81 | 6 | 19:10 | 1.1524 | 6/2 | 3 | moderate | |||
Female | 73 | 3 | 13:20 | 0.4838 | 3/2 | 0 | none |
Protein Family | CTRL 1134511 | CTRL 12449/11 | CTRL 3887/11 | CTRL 6614/11 | CTRL 6878/11 | PD 10158/11 | PD 10488/11 | PD 11321/09 | PD 11749/09 | PD 4406/09 |
---|---|---|---|---|---|---|---|---|---|---|
ATP Synthase | 16.59 | 16.53 | 13.24 | 15.49 | 13.76 | 12.30 | 12.03 | 14.17 | 14.82 | 16.51 |
TIM/TOM complex | 0.23 | 0.31 | 0.30 | 0.29 | 0.26 | 0.29 | 0.11 | 0.27 | 0.27 | 0.38 |
Entry | Protein Names | Gene Names | Subcellular Location [CC] |
---|---|---|---|
P21926 | CD9 antigen (5H9 antigen) * | CD9 MIC3 TSPAN29 GIG2 | Cell membrane |
O00142 | Thymidine kinase 2, mitochondrial | TK2 | Mitochondrion. |
Q9BZE1 | 39S ribosomal protein L37, mitochondrial | MRPL37 MRPL2 RPML2 HSPC235 | Mitochondrion |
Q9BYT8 | Neurolysin, mitochondrial | NLN AGTBP KIAA1226 | Mitochondrion intermembrane space |
P33316 | Deoxyuridine 5′-triphosphate nucleotidohydrolase, mitochondrial | DUT | Nucleus |
Q99798 | Aconitate hydratase, mitochondrial | ACO2 | Mitochondrion |
P80404 | 4-aminobutyrate aminotransferase, mitochondrial | ABAT GABAT | Mitochondrion matrix. |
Q9H6V9 | Lipid droplet-associated hydrolase | LDAH C2orf43 | Lipid droplet |
P40926 | Malate dehydrogenase, mitochondrial | MDH2 | Mitochondrion matrix |
P42126 | Enoyl-CoA delta isomerase 1, mitochondrial | ECI1 DCI | Mitochondrion matrix |
Q92665 | 28S ribosomal protein S31, mitochondrial | MRPS31 IMOGN38 | Mitochondrion |
O00330 | Pyruvate dehydrogenase protein X component, mitochondrial | PDHX PDX1 | Mitochondrion matrix. |
P31930 | Cytochrome b-c1 complex subunit 1, mitochondrial | UQCRC1 | Mitochondrion inner membrane |
Q96GW9 | Methionine--tRNA ligase, mitochondrial | MARS2 | Mitochondrion matrix |
O14744 | Protein arginine N-methyltransferase 5 | PRMT5 HRMT1L5 IBP72 JBP1 SKB1 | Cytoplasm |
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Plum, S.; Eggers, B.; Helling, S.; Stepath, M.; Theiss, C.; Leite, R.E.P.; Molina, M.; Grinberg, L.T.; Riederer, P.; Gerlach, M.; et al. Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease. Cells 2020, 9, 2580. https://doi.org/10.3390/cells9122580
Plum S, Eggers B, Helling S, Stepath M, Theiss C, Leite REP, Molina M, Grinberg LT, Riederer P, Gerlach M, et al. Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease. Cells. 2020; 9(12):2580. https://doi.org/10.3390/cells9122580
Chicago/Turabian StylePlum, Sarah, Britta Eggers, Stefan Helling, Markus Stepath, Carsten Theiss, Renata E. P. Leite, Mariana Molina, Lea T. Grinberg, Peter Riederer, Manfred Gerlach, and et al. 2020. "Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease" Cells 9, no. 12: 2580. https://doi.org/10.3390/cells9122580
APA StylePlum, S., Eggers, B., Helling, S., Stepath, M., Theiss, C., Leite, R. E. P., Molina, M., Grinberg, L. T., Riederer, P., Gerlach, M., May, C., & Marcus, K. (2020). Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease. Cells, 9(12), 2580. https://doi.org/10.3390/cells9122580