Metabolic characterization of intact cells reveals intracellular amyloid beta but not its precursor protein to reduce mitochondrial respiration

PLoS ONE

Volumn 11, Issue 12, 2016, Pages

  Schaefer, Patrick M ^a   Von Einem, Bjoern ^a   Walther, Paul ^a   Calzia, Enrico ^b   Von Arnim, Christine A F ^a  

^a UNIVERSITY OF ULM   (Germany)

^b UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE 1; ASPARTIC PROTEINASE; BACE1 PROTEIN, HUMAN; SECRETASE;

ANIMAL CELL; ARTICLE; BIOACCUMULATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; EMBRYO; HEK293 CELL LINE; HUMAN; HUMAN CELL; INTRACELLULAR TRANSPORT; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; MOUSE; NEUROBLASTOMA CELL; NONHUMAN; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; UPREGULATION; ALZHEIMER DISEASE; ANIMAL; CELL CULTURE; CELL RESPIRATION; CYTOPLASM; METABOLISM; MITOCHONDRION; NEUROBLASTOMA; PATHOLOGY; WESTERN BLOTTING;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; BLOTTING, WESTERN; CELL RESPIRATION; CELLS, CULTURED; CYTOPLASM; HEK293 CELLS; HUMANS; MEMBRANE POTENTIAL, MITOCHONDRIAL; MITOCHONDRIA; NEUROBLASTOMA;

EID: 85007315123     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0168157     Document Type: Article

References (62)

1. Rapoport SI, Horwitz B, Grady CL, Haxby JV, DeCarli C, Schapiro MB. Abnormal brain glucose metabolism in Alzheimer's disease, as measured by position emission tomography. Adv Exp Med Biol. 1991; 291:231-48. PMID: 1927686
2. Mattson MP, Pedersen WA, Duan W, Culmsee C, Camandola S. Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases. Ann N Y Acad Sci. 1999; 893:154-75. PMID: 10672236
3. Mosconi L, Pupi A, De Leon MJ. Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer's disease. Ann N Y Acad Sci. 2008; 1147:180-95. doi: 10.1196/annals.1427.007 PMID: 19076441
4. Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, et al. Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition. 2011; 27(1):3-20. doi: 10.1016/j.nut.2010.07.021 PMID: 21035308
5. Di Domenico F, Barone E, Perluigi M, Butterfield DA. The "Triangle of Death" in Alzheimer Disease Brain: The Aberrant Cross Talk Among Energy Metabolism, mTOR Signaling and Protein Homeostasis Revealed by Redox Proteomics. Antioxid Redox Signal. 2016.
6. Zhao W, Wang J, Varghese M, Ho L, Mazzola P, Haroutunian V, et al. Impaired mitochondrial energy metabolism as a novel risk factor for selective onset and progression of dementia in oldest-old subjects. Neuropsychiatr Dis Treat. 2015; 11:565-74. doi: 10.2147/NDT.S74898 PMID: 25784811
7. Perry EK, Perry RH, Tomlinson BE, Blessed G, Gibson PH. Coenzyme A-acetylating enzymes in Alzheimer's disease: possible cholinergic 'compartment' of pyruvate dehydrogenase. Neurosci Lett. 1980; 18(1):105-10. PMID: 6133246
8. Feldhaus P, Fraga DB, Ghedim FV, De Luca RD, Bruna TD, Heluany M, et al. Evaluation of respiratory chain activity in lymphocytes of patients with Alzheimer disease. Metab Brain Dis. 2011; 26(3):229-36. doi: 10.1007/s11011-011-9253-y PMID: 21789567
9. Sultana R, Butterfield DA. Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment. J Bioenerg Biomembr. 2009; 41(5):441-6. doi: 10.1007/s10863-009-9241-7 PMID: 19777328
10. de la Monte SM. Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease. Curr Alzheimer Res. 2012; 9(1):35-66. doi: 10.2174/156720512799015037 PMID: 22329651
11. Lin MT, Beal MF. Alzheimer's APP mangles mitochondria. Nat Med. 2006; 12(11):1241-3. doi: 10.1038/nm1106-1241 PMID: 17088888
12. Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, et al. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A. 2008; 105(35):13145-50. doi: 10.1073/pnas.0806192105 PMID: 18757748
13. Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol. 2003; 161(1):41-54. doi: 10.1083/jcb.200207030 PMID: 12695498
14. Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J Neurosci. 2006; 26(35):9057-68. doi: 10.1523/JNEUROSCI.1469-06. 2006 PMID: 16943564
15. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science. 2004; 304(5669):448-52. doi: 10.1126/science.1091230 PMID: 15087549
16. Luque-Contreras D, Carvajal K, Toral-Rios D, Franco-Bocanegra D, Campos-Peña V. Oxidative stress and metabolic syndrome: cause or consequence of Alzheimer's disease? Oxid Med Cell Longev. 2014; 2014:497802. doi: 10.1155/2014/497802 PMID: 24683436
17. Aleardi AM, Benard G, Augereau O, Malgat M, Talbot JC, Mazat JP, et al. Gradual alteration of mitochondrial structure and function by beta-amyloids: importance of membrane viscosity changes, energy deprivation, reactive oxygen species production, and cytochrome c release. J Bioenerg Biomembr. 2005; 37(4):207-25. doi: 10.1007/s10863-005-6631-3 PMID: 16167177
18. Kwon B, Gamache T, Lee HK, Querfurth HW. Synergistic effects of β-amyloid and ceramide-induced insulin resistance on mitochondrial metabolism in neuronal cells. Biochim Biophys Acta. 2015; 1852 (9):1810-23. doi: 10.1016/j.bbadis.2015.05.012 PMID: 26022371
19. Bobba A, Amadoro G, Valenti D, Corsetti V, Lassandro R, Atlante A. Mitochondrial respiratory chain Complexes I and IV are impaired by β-amyloid via direct interaction and through Complex I-dependent ROS production, respectively. Mitochondrion. 2013; 13(4):298-311. doi: 10.1016/j.mito.2013.03.008 PMID: 23562762
20. Rijal Upadhaya A, Scheibe F, Kosterin I, Abramowski D, Gerth J, Kumar S, et al. The type of Aβ-related neuronal degeneration differs between amyloid precursor protein (APP23) and amyloid β-peptide (APP48) transgenic mice. Acta Neuropathol Commun. 2013; 1:77. doi: 10.1186/2051-5960-1-77 PMID: 24252227
21. Xie H, Guan J, Borrelli LA, Xu J, Serrano-Pozo A, Bacskai BJ. Mitochondrial alterations near amyloid plaques in an Alzheimer's disease mouse model. J Neurosci. 2013; 33(43):17042-51. doi: 10.1523/JNEUROSCI.1836-13.2013 PMID: 24155308
22. Sarkar S, Jun S, Simpkins JW. Estrogen amelioration of Aβ-induced defects in mitochondria is mediated by mitochondrial signaling pathway involving ERβ, AKAP and Drp1. Brain Res. 2015; 1616:101-11. doi: 10.1016/j.brainres.2015.04.059 PMID: 25964165
23. Gray NE, Sampath H, Zweig JA, Quinn JF, Soumyanath A. Centella asiatica Attenuates Amyloid-β- Induced Oxidative Stress and Mitochondrial Dysfunction. J Alzheimers Dis. 2015; 45(3):933-46. doi: 10.3233/JAD-142217 PMID: 25633675
24. Cha MY, Han SH, Son SM, Hong HS, Choi YJ, Byun J, et al. Mitochondria-specific accumulation of amyloid β induces mitochondrial dysfunction leading to apoptotic cell death. PLoS One. 2012; 7(4): e34929. doi: 10.1371/journal.pone.0034929 PMID: 22514691
25. Eckert SH, Eckmann J, Renner K, Eckert GP, Leuner K, Muller WE. Dimebon ameliorates amyloid-β induced impairments of mitochondrial form and function. J Alzheimers Dis. 2012; 31(1):21-32. doi: 10.3233/JAD-2012-120310 PMID: 22475801
26. Rhein V, Baysang G, Rao S, Meier F, Bonert A, Müller-Spahn F, et al. Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells. Cell Mol Neurobiol. 2009; 29(6-7):1063-71. doi: 10.1007/s10571-009-9398-y PMID: 19350381
27. Krako N, Magnifico MC, Arese M, Meli G, Forte E, Lecci A, et al. Characterization of mitochondrial dysfunction in the 7PA2 cell model of Alzheimer's disease. J Alzheimers Dis. 2013; 37(4):747-58. doi: 10.3233/JAD-130728 PMID: 23948918
28. Chang KL, Pee HN, Tan WP, Dawe GS, Holmes E, Nicholson JK, et al. Metabolic profiling of CHOAβPP695 cells revealed mitochondrial dysfunction prior to amyloid-β pathology and potential therapeutic effects of both PPARγ and PPARα Agonisms for Alzheimer's disease. J Alzheimers Dis. 2015; 44 (1):215-31. doi: 10.3233/JAD-140429 PMID: 25201780
29. Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, et al. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci U S A. 2008; 105(49):19318-23. doi: 10.1073/pnas.0804871105 PMID: 19050078
30. Kinoshita A, Whelan CM, Smith CJ, Mikhailenko I, Rebeck GW, Strickland DK, et al. Demonstration by fluorescence resonance energy transfer of two sites of interaction between the low-density lipoprotein receptor-related protein and the amyloid precursor protein: role of the intracellular adapter protein Fe65. J Neurosci. 2001; 21(21):8354-61. PMID: 11606623
31. von Einem B, Wahler A, Schips T, Serrano-Pozo A, Proepper C, Boeckers TM, et al. The Golgi-Localized γ-Ear-Containing ARF-Binding (GGA) Proteins Alter Amyloid-β Precursor Protein (APP) Processing through Interaction of Their GAE Domain with the Beta-Site APP Cleaving Enzyme 1 (BACE1). PLoS One. 2015; 10(6):e0129047. doi: 10.1371/journal.pone.0129047 PMID: 26053850
32. Wilkat M, Herdoiza E, Forsbach-Birk V, Walther P, Essig A. Electron tomography and cryo-SEM characterization reveals novel ultrastructural features of host-parasite interaction during Chlamydia abortus infection. Histochem Cell Biol. 2014; 142(2):171-84. doi: 10.1007/s00418-014-1189-y PMID: 24522393
33. Walther P, Schmid E, Höhn K. High-pressure freezing for scanning transmission electron tomography analysis of cellular organelles. Methods Mol Biol. 2013; 931:525-35. doi: 10.1007/978-1-62703-056-4-28 PMID: 23027022
34. Buser C, Walther P. Freeze-substitution: the addition of water to polar solvents enhances the retention of structure and acts at temperatures around -60 degrees C. J Microsc. 2008; 230(Pt 2):268-77. doi: 10.1111/j.1365-2818.2008.01984.x PMID: 18445157
35. Parihar MS, Brewer GJ. Mitoenergetic failure in Alzheimer disease. Am J Physiol Cell Physiol. 2007; 292(1):C8-23. doi: 10.1152/ajpcell.00232.2006 PMID: 16807300
36. Bélanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 2011; 14(6):724-38. doi: 10.1016/j.cmet.2011.08.016 PMID: 22152301
37. Kaminsky YG, Tikhonova LA, Kosenko EA. Critical analysis of Alzheimer's amyloid-beta toxicity to mitochondria. Front Biosci (Landmark Ed). 2015; 20:173-97.
38. Anandatheerthavarada HK, Devi L. Amyloid precursor protein and mitochondrial dysfunction in Alzheimer's disease. Neuroscientist. 2007; 13(6):626-38. doi: 10.1177/1073858407303536 PMID: 17911214
39. Rhein V, Giese M, Baysang G, Meier F, Rao S, Schulz KL, et al. Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure. PLoS One. 2010; 5(8):e12359. doi: 10.1371/journal.pone.0012359 PMID: 20808761
40. Lee I, Bender E, Arnold S, Kadenbach B. New control of mitochondrial membrane potential and ROS formation-a hypothesis. Biol Chem. 2001; 382(12):1629-36. doi: 10.1515/BC.2001.198 PMID: 11843176
41. Rottenberg H, Covian R, Trumpower BL. Membrane potential greatly enhances superoxide generation by the cytochrome bc1 complex reconstituted into phospholipid vesicles. J Biol Chem. 2009; 284 (29):19203-10. doi: 10.1074/jbc.M109.017376 PMID: 19478336
42. Sanderson TH, Reynolds CA, Kumar R, Przyklenk K, Hüttemann M. Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol. 2013; 47(1):9-23. doi: 10.1007/s12035-012-8344-z PMID: 23011809
43. Forkink M, Manjeri GR, Liemburg-Apers DC, Nibbeling E, Blanchard M, Wojtala A, et al. Mitochondrial hyperpolarization during chronic complex I inhibition is sustained by low activity of complex II, III, IV and V. Biochim Biophys Acta. 2014; 1837(8):1247-56. doi: 10.1016/j.bbabio.2014.04.008 PMID: 24769419
44. Hernandez-Zimbron LF, Luna-Muñoz J, Mena R, Vazquez-Ramirez R, Kubli-Garfias C, Cribbs DH, et al. Amyloid-β peptide binds to cytochrome C oxidase subunit 1. PLoS One. 2012; 7(8):e42344. doi: 10.1371/journal.pone.0042344 PMID: 22927926
45. Parks JK, Smith TS, Trimmer PA, Bennett JP, Parker WD. Neurotoxic Abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J Neurochem. 2001; 76(4):1050-6. PMID: 11181824
46. Horan MP, Pichaud N, Ballard JW. Review: quantifying mitochondrial dysfunction in complex diseases of aging. J Gerontol A Biol Sci Med Sci. 2012; 67(10):1022-35. doi: 10.1093/gerona/glr263 PMID: 22459622
47. Sheng B, Gong K, Niu Y, Liu L, Yan Y, Lu G, et al. Inhibition of gamma-secretase activity reduces Abeta production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer's disease. Free Radic Biol Med. 2009; 46 (10):1362-75. doi: 10.1016/j.freeradbiomed.2009.02.018 PMID: 19264123
48. Pohland M, Hagl S, Pellowska M, Wurglics M, Schubert-Zsilavecz M, Eckert GP. MH84: A Novel γ- Secretase Modulator/PPARγ Agonist-Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer's Disease. Neurochem Res. 2015.
49. Robinson A, Grösgen S, Mett J, Zimmer VC, Haupenthal VJ, Hundsdörfer B, et al. Upregulation of PGC-1α expression by Alzheimer's disease-associated pathway: presenilin 1/amyloid precursor protein (APP)/intracellular domain of APP. Aging Cell. 2014; 13(2):263-72. doi: 10.1111/acel.12183 PMID: 24304563
50. Landor SK, Mutvei AP, Mamaeva V, Jin S, Busk M, Borra R, et al. Hypo-and hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms. Proc Natl Acad Sci U S A. 2011; 108 (46):18814-9. doi: 10.1073/pnas.1104943108 PMID: 22065781
51. Devi L, Ohno M. Mitochondrial dysfunction and accumulation of the β-secretase-cleaved C-terminal fragment of APP in Alzheimer's disease transgenic mice. Neurobiol Dis. 2012; 45(1):417-24. doi: 10.1016/j.nbd.2011.09.001 PMID: 21933711
52. Weissmiller AM, Natera-Naranjo O, Reyna SM, Pearn ML, Zhao X, Nguyen P, et al. A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP. PLoS One. 2015; 10(2):e0118379. doi: 10.1371/journal.pone.0118379 PMID: 25710492
53. Mitani Y, Yarimizu J, Saita K, Uchino H, Akashiba H, Shitaka Y, et al. Differential effects between γ- secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J Neurosci. 2012; 32(6):2037-50. doi: 10.1523/JNEUROSCI.4264-11.2012 PMID: 22323718
54. Benilova I, Karran E, De Strooper B. The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci. 2012; 15(3):349-57. doi: 10.1038/nn.3028 PMID: 22286176
55. Pagani L, Eckert A. Amyloid-Beta interaction with mitochondria. Int J Alzheimers Dis. 2011; 2011:925050. doi: 10.4061/2011/925050 PMID: 21461357
56. Gouras GK, Tampellini D, Takahashi RH, Capetillo-Zarate E. Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer's disease. Acta Neuropathol. 2010; 119(5):523-41. doi: 10.1007/s00401-010-0679-9 PMID: 20354705
57. Gouras GK, Willén K, Faideau M. The inside-out amyloid hypothesis and synapse pathology in Alzheimer's disease. Neurodegener Dis. 2014; 13(2-3):142-6. doi: 10.1159/000354776 PMID: 24080821
58. Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, et al. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J. 2005; 19(14):2040-1. doi: 10.1096/fj.05-3735fje PMID: 16210396
59. Schreiner B, Hedskog L, Wiehager B, Ankarcrona M. Amyloid-β peptides are generated in mitochondria-associated endoplasmic reticulum membranes. J Alzheimers Dis. 2015; 43(2):369-74. doi: 10.3233/JAD-132543 PMID: 25096627
60. Pavlov PF, Wiehager B, Sakai J, Frykman S, Behbahani H, Winblad B, et al. Mitochondrial γ-secretase participates in the metabolism of mitochondria-associated amyloid precursor protein. FASEB J. 2011; 25(1):78-88. doi: 10.1096/fj.10-157230 PMID: 20833873
61. Lee EB, Zhang B, Liu K, Greenbaum EA, Doms RW, Trojanowski JQ, et al. BACE overexpression alters the subcellular processing of APP and inhibits Abeta deposition in vivo. J Cell Biol. 2005; 168(2):291-302. doi: 10.1083/jcb.200407070 PMID: 15642747
62. Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash GW, et al. Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer's transgenic mice. J Alzheimers Dis. 2010; 20 Suppl 2: S535-50.