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Early Expression of Parkinson’s Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats

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Abstract

PTEN-induced kinase 1 (PINK1) mutations are responsible for an autosomal recessive, familial form of Parkinson’s disease. PINK1 protein is a Ser/Thr kinase localized to the mitochondrial membrane and is involved in many processes including mitochondrial trafficking, mitophagy, and proteasomal function. Using a new PINK1 knockout (PINK1 KO) rat model, we found altered brain metabolomic markers using magnetic resonance spectroscopy, identified changes in mitochondrial pathways with quantitative proteomics using sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry, and demonstrated mitochondrial functional alterations through measurement of oxygen consumption and acidification rates. The observed alterations included reduced creatine, decreased levels of complex I of the electron transport chain, and increased proton leak in the electron transport chain in PINK1 KO rat brains. In conjunction, these results demonstrate metabolomic and mitochondrial alterations occur during the asymptomatic phase of Parkinson’s disease in this model. These results indicate both potential early diagnostic markers and therapeutic pathways that can be used in PD.

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References

  1. Parker WD Jr, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218

    Article  CAS  PubMed  Google Scholar 

  2. Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD (1989) Mitochondrial complex I deficiency in Parkinson’s disease. Lancet 1:1269

    Article  CAS  PubMed  Google Scholar 

  3. Keeney PM, Xie J, Capaldi RA, Bennett JP Jr (2006) Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 26:5256–5264

    Article  CAS  PubMed  Google Scholar 

  4. Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4:600–609

    Article  CAS  PubMed  Google Scholar 

  5. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T et al (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38:515–517

    Article  CAS  PubMed  Google Scholar 

  6. Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38:518–520

    Article  CAS  PubMed  Google Scholar 

  7. Miller GW (2007) Paraquat: the red herring of Parkinson’s disease research. Toxicol Sci Off J Soc Toxicol 100:1–2

    Article  CAS  Google Scholar 

  8. Fornai F, Schluter OM, Lenzi P, Gesi M, Ruffoli R, Ferrucci M, Lazzeri G, Busceti CL, Pontarelli F, Battaglia G et al (2005) Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc Natl Acad Sci U S A 102:3413–3418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306

    Article  CAS  PubMed  Google Scholar 

  10. Somayajulu-Nitu M, Sandhu JK, Cohen J, Sikorska M, Sridhar TS, Matei A, Borowy-Borowski H, Pandey S (2009) Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10. BMC Neurosci 10:88

    Article  PubMed  PubMed Central  Google Scholar 

  11. Crabtree DM, Zhang J (2012) Genetically engineered mouse models of Parkinson’s disease. Brain Res Bull 88:13–32

    Article  CAS  PubMed  Google Scholar 

  12. Dave KD, De Silva S, Sheth N, Ramboz S, Beck MJ, Quang C, Benkovic SA, Ahmad S, Sunkin S, Walker D, et al (2014) Phenotypic characterization of recessive gene knockout rat models of Parkinson’s disease. Neurobiol Dis in press.

  13. Gandhi S, Muqit MM, Stanyer L, Healy DG, Abou-Sleiman PM, Hargreaves I, Heales S, Ganguly M, Parsons L, Lees AJ et al (2006) PINK1 protein in normal human brain and Parkinson’s disease. Brain J Neurol 129:1720–1731

    Article  CAS  Google Scholar 

  14. Zhou C, Huang Y, Shao Y, May J, Prou D, Perier C, Dauer W, Schon EA, Przedborski S (2008) The kinase domain of mitochondrial PINK1 faces the cytoplasm. Proc Natl Acad Sci U S A 105:12022–12027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Scarffe LA, Stevens DA, Dawson VL, Dawson TM (2014) Parkin and PINK1: much more than mitophagy. Trends Neurosci 37:315–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Guo M (2012) Drosophila as a model to study mitochondrial dysfunction in Parkinson’s disease. Cold Spring Harb Perspect Med 2(11). doi:10.1101/cshperspect.a009944

  17. Xiong H, Wang D, Chen L, Choo YS, Ma H, Tang C, Xia K, Jiang W, Ronai Z, Zhuang X, Zhang Z (2009) Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. J Clin Invest 119:650–660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Paxinos G, Watson C (2007) The Rat Brain in Stereotactic Coordinates, 6 edn. Academic Press

  19. Hsu SM, Raine L, Fanger H (1981) The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol 75:816–821

    Article  CAS  PubMed  Google Scholar 

  20. Gundersen HJ, Jensen EB (1987) The efficiency of systematic sampling in stereology and its prediction. J Microsc 147:229–263

    Article  CAS  PubMed  Google Scholar 

  21. Elozory DT, Kramer KA, Chaudhuri B, Bonam OP, Goldgof DB, Hall LO, Mouton PR (2012) Automatic section thickness determination using an absolute gradient focus function. J Microsc 248:245–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. West MJ, Slomianka L, Gundersen HJ (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482–497

    Article  CAS  PubMed  Google Scholar 

  23. Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, Pierce K (2011) Neuron number and size in prefrontal cortex of children with autism. JAMA J Am Med Assoc 306:2001–2010

    Article  CAS  Google Scholar 

  24. Mouton PR, Kelley-Bell B, Tweedie D, Spangler EL, Perez E, Carlson OD, Short RG, deCabo R, Chang J, Ingram DK, et al (2012) The effects of age and lipopolysaccharide (LPS)-mediated peripheral inflammation on numbers of central catecholaminergic neurons. Neurobiol Aging 33:423 e427-436

  25. Bottomley PA (1987) Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci 508:333–348

    Article  CAS  PubMed  Google Scholar 

  26. Ratiney H, Coenradie Y, Cavassila S, van Ormondt D, Graveron-Demilly D (2004) Time-domain quantitation of 1H short echo-time signals: background accommodation. MAGMA 16:284–296

    Article  CAS  PubMed  Google Scholar 

  27. Ratiney H, Sdika M, Coenradie Y, Cavassila S, van Ormondt D, Graveron-Demilly D (2005) Time-domain semi-parametric estimation based on a metabolite basis set. NMR Biomed 18:1–13

    Article  CAS  PubMed  Google Scholar 

  28. Gillet LC, Navarro P, Tate S, Rost H, Selevsek N, Reiter L, Bonner R, Aebersold R (2012) Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteomics MCP 11:O111.016717

    Article  PubMed  Google Scholar 

  29. Stauch KL, Purnell PR, Fox HS (2014) Quantitative proteomics of synaptic and nonsynaptic mitochondria: insights for synaptic mitochondrial vulnerability. J Proteome Res 13(5):2620–2636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Villeneuve L, Tiede LM, Morsey B, Fox HS (2013) Quantitative proteomics reveals oxygen-dependent changes in neuronal mitochondria affecting function and sensitivity to rotenone. J Proteome Res 12:4599–4606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Scopes RK (1974) Measurement of protein by spectrophotometry at 205 nm. Anal Biochem 59:277–282

    Article  CAS  PubMed  Google Scholar 

  32. Kayala MA, Baldi P (2012) Cyber-T web server: differential analysis of high-throughput data. Nucleic Acids Res 40:W553–W559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Baldi P, Long AD (2001) A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics 17:509–519

    Article  CAS  PubMed  Google Scholar 

  34. Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N, Braisted J, Klapa M, Currier T, Thiagarajan M et al (2003) TM4: a free, open-source system for microarray data management and analysis. BioTechniques 34:374–378

    CAS  PubMed  Google Scholar 

  35. Kramer A, Green J, Pollard J Jr, Tugendreich S (2014) Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30(4):523–530

    Article  PubMed  Google Scholar 

  36. Rogers GW, Brand MD, Petrosyan S, Ashok D, Elorza AA, Ferrick DA, Murphy AN (2011) High throughput microplate respiratory measurements using minimal quantities of isolated mitochondria. PLoS One 6:e21746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chance B, Williams GR (1956) The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem 17:65–134

    CAS  PubMed  Google Scholar 

  38. Chang DT, Reynolds IJ (2006) Mitochondrial trafficking and morphology in healthy and injured neurons. Prog Neurobiol 80:241–268

    Article  CAS  PubMed  Google Scholar 

  39. Brand MD, Nicholls DG (2011) Assessing mitochondrial dysfunction in cells. Biochem J 435:297–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cooper O, Seo H, Andrabi S, Guardia-Laguarta C, Graziotto J, Sundberg M, McLean JR, Carrillo-Reid L, Xie Z, Osborn T et al (2012) Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson’s disease. Sci Transl Med 4:141ra190

    Article  Google Scholar 

  41. Chen PE, Geballe MT, Stansfeld PJ, Johnston AR, Yuan H, Jacob AL, Snyder JP, Traynelis SF, Wyllie DJ (2005) Structural features of the glutamate binding site in recombinant NR1/NR2A N-methyl-D-aspartate receptors determined by site-directed mutagenesis and molecular modeling. Mol Pharmacol 67:1470–1484

    Article  CAS  PubMed  Google Scholar 

  42. Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163

    CAS  PubMed  Google Scholar 

  43. Kumari N, Prentice H, Wu JY (2013) Taurine and its neuroprotective role. Adv Exp Med Biol 775:19–27

    Article  CAS  PubMed  Google Scholar 

  44. Dominy J Jr, Thinschmidt JS, Peris J, Dawson R Jr, Papke RL (2004) Taurine-induced long-lasting potentiation in the rat hippocampus shows a partial dissociation from total hippocampal taurine content and independence from activation of known taurine transporters. J Neurochem 89:1195–1205

    Article  CAS  PubMed  Google Scholar 

  45. Foos TM, Wu JY (2002) The role of taurine in the central nervous system and the modulation of intracellular calcium homeostasis. Neurochem Res 27:21–26

    Article  CAS  PubMed  Google Scholar 

  46. Leon R, Wu H, Jin Y, Wei J, Buddhala C, Prentice H, Wu JY (2009) Protective function of taurine in glutamate-induced apoptosis in cultured neurons. J Neurosci Res 87:1185–1194

    Article  CAS  PubMed  Google Scholar 

  47. Hansen SH, Andersen ML, Birkedal H, Cornett C, Wibrand F (2006) The important role of taurine in oxidative metabolism. Adv Exp Med Biol 583:129–135

    Article  CAS  PubMed  Google Scholar 

  48. Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99

    Article  CAS  PubMed  Google Scholar 

  49. Hansen SH, Andersen ML, Cornett C, Gradinaru R, Grunnet N (2010) A role for taurine in mitochondrial function. J Biomed Sci 17(Suppl 1):S23

    Article  PubMed  PubMed Central  Google Scholar 

  50. Engelborghs S, Marescau B, De Deyn PP (2003) Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson’s disease. Neurochem Res 28:1145–1150

    Article  CAS  PubMed  Google Scholar 

  51. Ghisla S, Thorpe C (2004) Acyl-CoA dehydrogenases. A mechanistic overview. Eur J Biochem FEBS 271:494–508

    Article  CAS  Google Scholar 

  52. Gualano B, de Salles PV, Roschel H, Lugaresi R, Dorea E, Artioli GG, Lima FR, da Silva ME, Cunha MR, Seguro AC et al (2011) Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial. Eur J Appl Physiol 111:749–756

    Article  CAS  PubMed  Google Scholar 

  53. NINDS NET-PD Investigators (2006) A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology 66:664–671

    Article  Google Scholar 

  54. NINDS NET-PD Investigators (2008) A pilot clinical trial of creatine and minocycline in early Parkinson disease: 18-month results. Clin Neuropharmacol 31:141–150

    Article  Google Scholar 

  55. Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M, Gekeler F, Muller-Myhsok B, Gasser T, Tatsch K, Klopstock T (2006) Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 67:1262–1264

    Article  CAS  PubMed  Google Scholar 

  56. Adhihetty PJ, Beal MF (2008) Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseases. Neruomol Med 10:275–290

    Article  CAS  Google Scholar 

  57. Rakshi JS, Uema T, Ito K, Bailey DL, Morrish PK, Ashburner J, Dagher A, Jenkins IH, Friston KJ, Brooks DJ (1999) Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson’s disease A 3D [(18)F]dopa-PET study. Brain J Neurol 122(Pt 9):1637–1650

    Article  Google Scholar 

  58. Graham JW, Williams TC, Morgan M, Fernie AR, Ratcliffe RG, Sweetlove LJ (2007) Glycolytic enzymes associate dynamically with mitochondria in response to respiratory demand and support substrate channeling. Plant Cell 19:3723–3738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Yao Z, Gandhi S, Burchell VS, Plun-Favreau H, Wood NW, Abramov AY (2011) Cell metabolism affects selective vulnerability in PINK1-associated Parkinson’s disease. J Cell Sci 124:4194–4202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mazzio E, Soliman KF (2003) The role of glycolysis and gluconeogenesis in the cytoprotection of neuroblastoma cells against 1-methyl 4-phenylpyridinium ion toxicity. Neurotoxicology 24:137–147

    Article  CAS  PubMed  Google Scholar 

  61. Buono P, D’Armiento FP, Terzi G, Alfieri A, Salvatore F (2001) Differential distribution of aldolase A and C in the human central nervous system. J Neurocytol 30:957–965

    Article  CAS  PubMed  Google Scholar 

  62. Stowers RS, Megeath LJ, Gorska-Andrzejak J, Meinertzhagen IA, Schwarz TL (2002) Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36:1063–1077

    Article  CAS  PubMed  Google Scholar 

  63. Guo X, Macleod GT, Wellington A, Hu F, Panchumarthi S, Schoenfield M, Marin L, Charlton MP, Atwood HL, Zinsmaier KE (2005) The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 47:379–393

    Article  CAS  PubMed  Google Scholar 

  64. Ma H, Cai Q, Lu W, Sheng ZH, Mochida S (2009) KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons. J Neurosci 29:13019–13029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Lammermann K, Brunner B, Kurz-Drexler A, Vogel F, Reichert AS et al (2009) Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 284:22938–22951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Giordano S, Darley-Usmar V, Zhang J (2014) Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease. Redox Biol 2:82–90

    Article  CAS  PubMed  Google Scholar 

  67. Chen JF, Xu K, Petzer JP, Staal R, Xu YH, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli N Jr, Schwarzschild MA (2001) Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson’s disease. J Neurosci 21:RC143

    CAS  PubMed  Google Scholar 

  68. Xu K, Xu YH, Chen JF, Schwarzschild MA (2002) Caffeine’s neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity shows no tolerance to chronic caffeine administration in mice. Neurosci Lett 322:13–16

    Article  CAS  PubMed  Google Scholar 

  69. Kalda A, Yu L, Oztas E, Chen JF (2006) Novel neuroprotection by caffeine and adenosine A(2A) receptor antagonists in animal models of Parkinson’s disease. J Neurol Sci 248:9–15

    Article  CAS  PubMed  Google Scholar 

  70. Popat RA, Van Den Eeden SK, Tanner CM, Kamel F, Umbach DM, Marder K, Mayeux R, Ritz B, Ross GW, Petrovitch H et al (2011) Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease. Eur J Neurol Off J Eur Fed Neurol Soc 18:756–765

    CAS  Google Scholar 

  71. Speakman JR, Talbot DA, Selman C, Snart S, McLaren JS, Redman P, Krol E, Jackson DM, Johnson MS, Brand MD (2004) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3:87–95

    Article  CAS  PubMed  Google Scholar 

  72. Ivanov AS, Putvinskii AV, Antonov VF, Vladimirov IA (1977) Magnitude of the protein permeability of liposomes following photoperoxidation of lipids. Biofizika 22:621–624

    CAS  PubMed  Google Scholar 

  73. Skulachev VP (1996) Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants. Q Rev Biophys 29:169–202

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank the Proteomics Core Facility members at the University of Nebraska Medical Center, under the direction of Dr. Pawel Ciborowski, for all their support and aid in the proteomics experiments, and Dr. Kelly Stauch and Robin Taylor for their assistance. and Dr. Kelly Stauch and Robin Taylor for their assistance.

Funding Sources

This work was funded by the National Institute of Health (NIH) MH073490 and NIH MH062261.

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Authors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center—DRC1 3008, Omaha, NE, 68198-5800, USA

    Lance M. Villeneuve, Phillip R. Purnell, Michael D. Boska & Howard S. Fox

  2. Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Michael D. Boska

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  1. Lance M. Villeneuve
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  2. Phillip R. Purnell
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Correspondence to Howard S. Fox.

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Supplemental Fig. 1

Cortical metabolomic measurement of PINK1-deficient rats. Metabolites were measured in the cortex using magnetic resonance spectroscopy (MRS) in vivo. Measurements of alanine (A), aspartate (B), choline (C), creatine (D), GABA (E), glutamate (F), glutamine (G), glycerophosphocholine (H), glycine (I), lactate (J), N-acetylaspartate (K), and taurine (L) were taken at 10 (2.5 weeks) weeks of age every 4 weeks until 34 (8.5 months) weeks of age. The measurements were normalized to the total metabolite measurement. Statistical significance was determined by a repeated measures two-way ANOVA. Sidak’s post hoc comparison test was used to determine difference at any given time point. Listed p values correspond to p values generated by ANOVA. *p ≤ 0.05 on Sidak’s post hoc comparison test. n = 6 for cortical LEH and PINK1 KO animals. (GIF 66 kb)

High Resolution Image (TIFF 212 kb)

Supplemental Fig. 2

Striatal metabolomic measurements of PINK1-deficient rats. Metabolites were measured in the cortex and striatum using magnetic resonance spectroscopy (MRS) in vivo. Measurements of alanine (A), choline (B), GABA (C), glutamate (D), glutamine (E), glycerophosphocholine (F), glycine (G), lactate (H), myoinositol (I), and N-acetylaspartate (J) were taken at 10 (2.5 weeks) weeks of age every 4 weeks until 34 (8.5 months) weeks of age. The measurements were normalized to the total metabolite measurement. Statistical significance was determined by a repeated measures two-way ANOVA. Sidak’s post hoc comparison test was used to determine difference at any given time point. Listed p values correspond to p values generated by ANOVA. *p ≤ 0.05 on Sidak’s post hoc comparison test. n = 6 and n = 5 for striatal LEH and PINK1 KO animals, respectively. (GIF 56 kb)

High Resolution Image (TIFF 208 kb)

Supplemental Table 1

List of significantly altered proteins in the PINK1 KO rat brain. Protein expression was uploaded into CyberT (http://cybert.ics.uci.edu/). A Bayesian analysis of the proteins were performed with the Bayesian coefficient = 12. Multiple testing correction was applied using the cumulative posterior probability of differential expression (Cum. PPDE). The false discovery rate (α) was set to 0.05 (Cum. PPDE\( \ge \)0.95). (XLSX 19 kb)

Supplemental Table 2

List of all measurements made during SWATH mass spectrometry analysis. The expression levels are listed for each protein and animal. Log2 ratios are displayed for each protein. The p value corresponds to the p value generated by the Bayesian analysis in CyberT (http://cybert.ics.uci.edu/). Cum. PPDE cumulative posterior probability of differential expression. n = 4 animals per experimental group. (XLSX 601 kb)

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Villeneuve, L.M., Purnell, P.R., Boska, M.D. et al. Early Expression of Parkinson’s Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats. Mol Neurobiol 53, 171–186 (2016). https://doi.org/10.1007/s12035-014-8927-y

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