[en] OBJECTIVES: Normal cellular function requires a rate of ATP production sufficient to meet demand. In most neurodegenerative diseases (including Amyotrophic Lateral Sclerosis [ALS]), mitochondrial dysfunction is postulated raising the possibility of impaired ATP production and a need for compensatory maneuvers to sustain the ATP production/demand balance. We investigated intermediary metabolism of neurons expressing familial ALS (fALS) genes and interrogated the functional consequences of glycolysis genes in fitness assays and neuronal survival. METHODS: We created a pure neuronal model system for isotopologue investigations of fuel utilization. In a yeast platform we studied the functional contributions of glycolysis genes in a growth fitness assay iafter expressing of a fALS gene. RESULTS: We find in our rodent models of fALS, a reduction in neuronal lactate production with maintained or enhanced activity of the neuronal citric acid cycle. This rewiring of metabolism is associated with normal ATP levels, bioenergetics, and redox status, thus supporting the notion that gross mitochondrial function is not compromised in neurons soon after expressing fALS genes. Genetic loss-of-function manipulation of individual steps in the glycolysis and the pentose phosphate pathway blunt the negative phenotypes seen in various fALS models. CONCLUSIONS: We propose that neurons adjust fuel utilization in the setting of neurodegenerative disease-associated alteration in mitochondrial function in a baleful manner and targeting this process can be healthful.
Disciplines :
Neurology
Author, co-author :
Riechers, Sean-Patrick Hermann ; Department of Neurology, Feinberg School of Medicine, Northwestern University, United States.
Mojsilovic-Petrovic, Jelena
Belton, Tayler B.
Chakrabarty, Ram P.
Garjani, Mehraveh
Medvedeva, Valentina
Dalton, Casey
Wong, Yvette C.
Chandel, Navdeep S.
Dienel, Gerald
Kalb, Robert G.
External co-authors :
yes
Language :
English
Title :
Neurons undergo pathogenic metabolic reprogramming in models of familial ALS.
Archer, S.L., Mitochondrial dynamics–mitochondrial fission and fusion in human diseases. The New England Journal of Medicine 369:23 (2013), 2236–2251, 10.1056/NEJMra1215233.
Lin, M.T., Beal, M.F., Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:7113 (2006), 787–795, 10.1038/nature05292.
Casajus Pelegay, E., Puzzo, F., Yilmazer, A., Cagin, U., Targeting mitochondrial defects to increase longevity in animal models of neurodegenerative diseases. Advances in Experimental Medicine & Biology 1134:Chapter 5 (2019), 89–110, 10.1007/978-3-030-12668-1_5.
Area-Gomez, E., Guardia-Laguarta, C., Schon, E.A., Przedborski, S., Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas. The Journal of Clinical Investigation 129:1 (2019), 34–45, 10.1172/JCI120848.
Gao, J., Wang, L., Yan, T., Perry, G., Wang, X., TDP-43 proteinopathy and mitochondrial abnormalities in neurodegeneration. Molecular and Cellular Neurosciences, 100, 2019, 103396, 10.1016/j.mcn.2019.103396.
Wu, Y., Chen, M., Jiang, J., Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling. Mitochondrion 49 (2019), 35–45, 10.1016/j.mito.2019.07.003.
Rangaraju, V., Lewis, T.L., Hirabayashi, Y., Bergami, M., Motori, E., Cartoni, R., et al. Pleiotropic mitochondria: the influence of mitochondria on neuronal development and disease. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 39:42 (2019), 8200–8208, 10.1523/JNEUROSCI.1157-19.2019.
Cowan, K., Anichtchik, O., Luo, S., Mitochondrial integrity in neurodegeneration. CNS Neuroscience and Therapeutics 25:7 (2019), 825–836, 10.1111/cns.13105.
Mattiazzi, M., D'Aurelio, M., Gajewski, C.D., Martushova, K., Kiaei, M., Beal, M.F., et al. Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. The Journal of Biological Chemistry 277:33 (2002), 29626–29633, 10.1074/jbc.M203065200.
Dupuis, L., Oudart, H., René, F., Gonzalez de Aguilar, J.-L., Loeffler, J.-P., Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proceedings of the National Academy of Sciences of the United States of America 101:30 (2004), 11159–11164, 10.1073/pnas.0402026101.
Magrané, J., Sahawneh, M.A., Przedborski, S., Estévez, Á.G., Manfredi, G., Mitochondrial dynamics and bioenergetic dysfunction is associated with synaptic alterations in mutant SOD1 motor neurons. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 32:1 (2012), 229–242, 10.1523/JNEUROSCI.1233-11.2012.
Jung, C., Higgins, C.M.J., Xu, Z., Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis. Journal of Neurochemistry 83:3 (2002), 535–545, 10.1046/j.1471-4159.2002.01112.x.
Bowling, A.C., Schulz, J.B., Brown, R.H., Beal, M.F., Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. Journal of Neurochemistry 61:6 (1993), 2322–2325, 10.1111/j.1471-4159.1993.tb07478.x.
Kim, G.H., Kim, J.E., Rhie, S.J., Yoon, S., The role of oxidative stress in neurodegenerative diseases. Experimental Neurobiology 24:4 (2015), 325–340, 10.5607/en.2015.24.4.325.
Greco, V., Longone, P., Spalloni, A., Pieroni, L., Urbani, A., Crosstalk between oxidative stress and mitochondrial damage: focus on amyotrophic lateral sclerosis. Advances in Experimental Medicine & Biology 1158 (2019), 71–82, 10.1007/978-981-13-8367-0_5.
Pirie, E., Oh, C.-K., Zhang, X., Han, X., Cieplak, P., Scott, H.R., et al. S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD. Proceedings of the National Academy of Sciences of the United States of America, 118(11), 2021, 10.1073/pnas.2021368118.
Smith, E.F., Shaw, P.J., De Vos, K.J., The role of mitochondria in amyotrophic lateral sclerosis. Neuroscience Letters, 710, 2019, 132933, 10.1016/j.neulet.2017.06.052.
Marques, E.P., Wyse, A.T.S., Creatine as a neuroprotector: an actor that can play many parts. Neurotoxicity Research 36:2 (2019), 411–423, 10.1007/s12640-019-00053-7.
Vandoorne, T., De Bock, K., Van Den Bosch, L., Energy metabolism in ALS: an underappreciated opportunity?. Acta Neuropathologica 135:4 (2018), 489–509, 10.1007/s00401-018-1835-x.
Hardie, D.G., Ross, F.A., Hawley, S.A., AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nature Reviews Molecular Cell Biology 13:4 (2012), 251–262, 10.1038/nrm3311.
Dienel, G.A., Brain glucose metabolism: integration of energetics with function. Physiological Reviews 99:1 (2019), 949–1045, 10.1152/physrev.00062.2017.
Yu, Y., Herman, P., Rothman, D.L., Agarwal, D., Hyder, F., Evaluating the gray and white matter energy budgets of human brain function. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 38:8 (2018), 1339–1353, 10.1177/0271678X17708691.
Licznerski, P., Park, H.-A., Rolyan, H., Chen, R., Mnatsakanyan, N., Miranda, P., et al. ATP synthase c-subunit leak causes aberrant cellular metabolism in fragile X syndrome. Cell 182:5 (2020), 1170–1179, 10.1016/j.cell.2020.07.008.
Rangaraju, V., Calloway, N., Ryan, T.A., Activity-driven local ATP synthesis is required for synaptic function. Cell 156:4 (2014), 825–835, 10.1016/j.cell.2013.12.042.
Mann, K., Deny, S., Ganguli, S., Clandinin, T.R., Coupling of activity, metabolism and behaviour across the Drosophila brain. Nature 593:7858 (2021), 244–248, 10.1038/s41586-021-03497-0.
Hall, C.N., Klein-Flügge, M.C., Howarth, C., Attwell, D., Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 32:26 (2012), 8940–8951, 10.1523/JNEUROSCI.0026-12.2012.
DeBerardinis, R.J., Chandel, N.S., Fundamentals of cancer metabolism. Science Advances, 2(5), 2016, e1600200, 10.1126/sciadv.1600200.
Wood, T., Physiological functions of the pentose phosphate pathway. Cell Biochemistry and Function 4:4 (1986), 241–247, 10.1002/cbf.290040403.
Stanton, R.C., Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life 64:5 (2012), 362–369, 10.1002/iub.1017.
Kletzien, R.F., Harris, P.K., Foellmi, L.A., Glucose-6-phosphate dehydrogenase: a “housekeeping” enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress. Federation of American Societies for Experimental Biology Journal: Official Publication of the Federation of American Societies for Experimental Biology 8:2 (1994), 174–181, 10.1096/fasebj.8.2.8119488.
Denzel, M.S., Storm, N.J., Gutschmidt, A., Baddi, R., Hinze, Y., Jarosch, E., et al. Hexosamine pathway metabolites enhance protein quality control and prolong life. Cell 156:6 (2014), 1167–1178, 10.1016/j.cell.2014.01.061.
Slawson, C., Hart, G.W., O-GlcNAc signalling: implications for cancer cell biology. Nature Reviews Cancer 11:9 (2011), 678–684, 10.1038/nrc3114.
Wang, Z.V., Deng, Y., Gao, N., Pedrozo, Z., Li, D.L., Morales, C.R., et al. Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway. Cell 156:6 (2014), 1179–1192, 10.1016/j.cell.2014.01.014.
Xu, K., Yin, N., Peng, M., Stamatiades, E.G., Shyu, A., Li, P., et al. Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity. Science (New York, N.Y.) 371:6527 (2021), 405–410, 10.1126/science.abb2683.
Mojsilovic-Petrovic, J., Jeong, G.-B., Crocker, A., Arneja, A., David, S., Russell, D.S., et al. Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 26:36 (2006), 9250–9263, 10.1523/JNEUROSCI.1856-06.2006.
Waagepetersen, H.S., Sonnewald, U., Larsson, O.M., Schousboe, A., Compartmentation of TCA cycle metabolism in cultured neocortical neurons revealed by 13C MR spectroscopy. Neurochemistry International 36:4–5 (2000), 349–358, 10.1016/s0197-0186(99)00143-6.
Sonnewald, U., Hertz, L., Schousboe, A., Mitochondrial heterogeneity in the brain at the cellular level. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 18:3 (1998), 231–237, 10.1097/00004647-199803000-00001.
Israelson, A., Arbel, N., Da Cruz, S., Ilieva, H., Yamanaka, K., Shoshan-Barmatz, V., et al. Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS. Neuron 67:4 (2010), 575–587, 10.1016/j.neuron.2010.07.019.
Pasinelli, P., Belford, M.E., Lennon, N., Bacskai, B.J., Hyman, B.T., Trotti, D., et al. Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43:1 (2004), 19–30, 10.1016/j.neuron.2004.06.021.
Wang, W., Wang, L., Lu, J., Siedlak, S.L., Fujioka, H., Liang, J., et al. The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. Nature Medicine 22:8 (2016), 869–878, 10.1038/nm.4130.
Lai, J.C., Walsh, J.M., Dennis, S.C., Clark, J.B., Synaptic and non-synaptic mitochondria from rat brain: isolation and characterization. Journal of Neurochemistry 28:3 (1977), 625–631, 10.1111/j.1471-4159.1977.tb10434.x.
Leong, S.F., Lai, J.C., Lim, L., Clark, J.B., The activities of some energy-metabolising enzymes in nonsynaptic (free) and synaptic mitochondria derived from selected brain regions. Journal of Neurochemistry 42:5 (1984), 1306–1312, 10.1111/j.1471-4159.1984.tb02788.x.
Armakola, M., Higgins, M.J., Figley, M.D., Barmada, S.J., Scarborough, E.A., Diaz, Z., et al. Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models. Nature Genetics 44:12 (2012), 1302–1309, 10.1038/ng.2434.
Lim, M.A., Selak, M.A., Xiang, Z., Krainc, D., Neve, R.L., Kraemer, B.C., et al. Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 32:3 (2012), 1123–1141, 10.1523/JNEUROSCI.6554-10.2012.
Periz, G., Lu, J., Zhang, T., Kankel, M.W., Jablonski, A.M., Kalb, R., et al. Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription. PLoS Biology, 13(4), 2015, e1002114, 10.1371/journal.pbio.1002114.
Zhai, J., Zhang, L., Mojsilovic-Petrovic, J., Jian, X., Thomas, J., Homma, K., et al. Inhibition of cytohesins protects against genetic models of motor neuron disease. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 35:24 (2015), 9088–9105, 10.1523/JNEUROSCI.5032-13.2015.
Jablonski, A.M., Lamitina, T., Liachko, N.F., Sabatella, M., Lu, J., Zhang, L., et al. Loss of RAD-23 protects against models of motor neuron disease by enhancing mutant protein clearance. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 35:42 (2015), 14286–14306, 10.1523/JNEUROSCI.0642-15.2015.
Mojsilovic-Petrovic, J., Nedelsky, N., Boccitto, M., Mano, I., Georgiades, S.N., Zhou, W., et al. FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neuron diseases. Journal of Neuroscience 29:25 (2009), 8236–8247, 10.1523/JNEUROSCI.1805-09.2009.
Wen, X., Tan, W., Westergard, T., Krishnamurthy, K., Markandaiah, S.S., Shi, Y., et al. Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death. Neuron 84:6 (2014), 1213–1225, 10.1016/j.neuron.2014.12.010.
Ash, P.E.A., Bieniek, K.F., Gendron, T.F., Caulfield, T., Lin, W.-L., DeJesus-Hernandez, M., et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77:4 (2013), 639–646, 10.1016/j.neuron.2013.02.004.
Mizielinska, S., Grönke, S., Niccoli, T., Ridler, C.E., Clayton, E.L., Devoy, A., et al. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science (New York, N.Y.) 345:6201 (2014), 1192–1194, 10.1126/science.1256800.
Gupta, R., Lan, M., Mojsilovic-Petrovic, J., Choi, W.H., Safren, N., Barmada, S., et al. The proline/arginine dipeptide from hexanucleotide repeat ExpandedC9ORF72Inhibits the proteasome. eNeuro, 4(1), 2017, 10.1523/ENEURO.0249-16.2017 ENEURO.0249–16.2017.
Ghergurovich, J.M., García-Cañaveras, J.C., Wang, J., Schmidt, E., Zhang, Z., TeSlaa, T., et al. A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway. Nature Chemical Biology 16:7 (2020), 731–739, 10.1038/s41589-020-0533-x.
Lawton, K.A., Cudkowicz, M.E., Brown, M.V., Alexander, D., Caffrey, R., Wulff, J.E., et al. Biochemical alterations associated with ALS. Null 13:1 (2012), 110–118, 10.3109/17482968.2011.619197.
Wang, T., Liu, H., Itoh, K., Oh, S., Zhao, L., Murata, D., et al. C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly. Cell Metabolism 33:3 (2021), 531–539, 10.1016/j.cmet.2021.01.005.
Alves, C.J., Dariolli, R., Jorge, F.M., Monteiro, M.R., Maximino, J.R., Martins, R.S., et al. Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration. Frontiers in Cellular Neuroscience, 9, 2015, 289, 10.3389/fncel.2015.00289.
Genin, E.C., Madji Hounoum, B., Bannwarth, S., Fragaki, K., Lacas-Gervais, S., Mauri-Crouzet, A., et al. Mitochondrial defect in muscle precedes neuromuscular junction degeneration and motor neuron death in CHCHD10S59L/+ mouse. Acta Neuropathologica 138:1 (2019), 123–145, 10.1007/s00401-019-01988-z.
Kiskinis, E., Sandoe, J., Williams, L.A., Boulting, G.L., Moccia, R., Wainger, B.J., et al. Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell 14:6 (2014), 781–795, 10.1016/j.stem.2014.03.004.
Lee, H., Lee, J.J., Park, N.Y., Dubey, S.K., Kim, T., Ruan, K., et al. Multi-omic analysis of selectively vulnerable motor neuron subtypes implicates altered lipid metabolism in ALS. Nature Neuroscience 24:12 (2021), 1673–1685, 10.1038/s41593-021-00944-z.
Anderson, C.J., Bredvik, K., Burstein, S.R., Davis, C., Meadows, S.M., Dash, J., et al. ALS/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response. Acta Neuropathologica 138:1 (2019), 103–121, 10.1007/s00401-019-01989-y.
Wang, P., Deng, J., Dong, J., Liu, J., Bigio, E.H., Mesulam, M., et al. TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response. PLoS Genetics, 15(5), 2019, e1007947, 10.1371/journal.pgen.1007947.
Straub, I.R., Janer, A., Weraarpachai, W., Zinman, L., Robertson, J., Rogaeva, E., et al. Loss of CHCHD10-CHCHD2 complexes required for respiration underlies the pathogenicity of a CHCHD10 mutation in ALS. Human Molecular Genetics 27:1 (2018), 178–189, 10.1093/hmg/ddx393.
Baek, M., Choe, Y.-J., Bannwarth, S., Kim, J., Maitra, S., Dorn, G.W., et al. TDP-43 and PINK1 mediate CHCHD10S59L mutation-induced defects in Drosophila and in vitro. Nature Communications 12:1 (2021), 1924–2020, 10.1038/s41467-021-22145-9.
Yu, C.-H., Davidson, S., Harapas, C.R., Hilton, J.B., Mlodzianoski, M.J., Laohamonthonkul, P., et al. TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS. Cell 183:3 (2020), 636–649.e18, 10.1016/j.cell.2020.09.020.
Parone, P.A., Da Cruz, S., Han, J.S., McAlonis-Downes, M., Vetto, A.P., Lee, S.K., et al. Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 33:11 (2013), 4657–4671, 10.1523/JNEUROSCI.1119-12.2013.
Tan, W., Naniche, N., Bogush, A., Pedrini, S., Trotti, D., Pasinelli, P., Small peptides against the mutant SOD1/Bcl-2 toxic mitochondrial complex restore mitochondrial function and cell viability in mutant SOD1-mediated ALS. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 33:28 (2013), 11588–11598, 10.1523/JNEUROSCI.5385-12.2013.
Choi, S.Y., Lopez-Gonzalez, R., Krishnan, G., Phillips, H.L., Li, A.N., Seeley, W.W., et al. C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo. Nature Neuroscience 22:6 (2019), 851–862, 10.1038/s41593-019-0397-0.
Chang, Y.-C., Hung, W.-T., Chang, Y.-C., Chang, H.C., Wu, C.-L., Chiang, A.-S., et al. Pathogenic VCP/TER94 alleles are dominant actives and contribute to neurodegeneration by altering cellular ATP level in a Drosophila IBMPFD model. PLoS Genetics, 7(2), 2011, e1001288, 10.1371/journal.pgen.1001288.
Kim, N.C., Tresse, E., Kolaitis, R.-M., Molliex, A., Thomas, R.E., Alami, N.H., et al. VCP is essential for mitochondrial quality control by PINK1/Parkin and this function is impaired by VCP mutations. Neuron 78:1 (2013), 65–80, 10.1016/j.neuron.2013.02.029.
Bartolome, F., Wu, H.-C., Burchell, V.S., Preza, E., Wray, S., Mahoney, C.J., et al. Pathogenic VCP mutations induce mitochondrial uncoupling and reduced ATP levels. Neuron 78:1 (2013), 57–64, 10.1016/j.neuron.2013.02.028.
Li, S., Wu, Z., Li, Y., Tantray, I., De Stefani, D., Mattarei, A., et al. Altered MICOS morphology and mitochondrial ion homeostasis contribute to poly(GR) toxicity associated with C9-ALS/FTD. Cell Reports, 32(5), 2020, 107989, 10.1016/j.celrep.2020.107989.
Valbuena, G.N., Rizzardini, M., Cimini, S., Siskos, A.P., Bendotti, C., Cantoni, L., et al. Metabolomic analysis reveals increased aerobic glycolysis and amino acid deficit in a cellular model of amyotrophic lateral sclerosis. Molecular Neurobiology 53:4 (2016), 2222–2240, 10.1007/s12035-015-9165-7.
Allen, S.P., Rajan, S., Duffy, L., Mortiboys, H., Higginbottom, A., Grierson, A.J., et al. Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis. Neurobiology of Aging 35:6 (2014), 1499–1509, 10.1016/j.neurobiolaging.2013.11.025.
Manzo, E., Lorenzini, I., Barrameda, D., O'Conner, A.G., Barrows, J.M., Starr, A., et al. Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS. eLife, 8, 2019, 606, 10.7554/eLife.45114.
Tefera, T.W., Bartlett, K., Tran, S.S., Hodson, M.P., Borges, K., Impaired pentose phosphate pathway in the spinal cord of the hSOD1G93A mouse model of amyotrophic lateral sclerosis. Molecular Neurobiology 56:8 (2019), 5844–5855, 10.1007/s12035-019-1485-6.
Tefera, T.W., Borges, K., Neuronal glucose metabolism is impaired while astrocytic TCA cycling is unaffected at symptomatic stages in the hSOD1G93A mouse model of amyotrophic lateral sclerosis. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 39:9 (2019), 1710–1724, 10.1177/0271678X18764775.
Ziller, M.J., Ortega, J.A., Quinlan, K.A., Santos, D.P., Gu, H., Martin, E.J., et al. Dissecting the functional consequences of De Novo DNA methylation dynamics in human motor neuron differentiation and physiology. Cell Stem Cell, 2018, 10.1016/j.stem.2018.02.012.
Ortega, J.A., Daley, E.L., Kour, S., Samani, M., Tellez, L., Smith, H.S., et al. Nucleocytoplasmic proteomic analysis uncovers eRF1 and nonsense-mediated decay as modifiers of ALS/FTD C9orf72 toxicity. Neuron 106:1 (2020), 90–107.e13, 10.1016/j.neuron.2020.01.020.
Pellerin, L., Magistretti, P.J., Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proceedings of the National Academy of Sciences of the United States of America 91:22 (1994), 10625–10629, 10.1073/pnas.91.22.10625.
Jolivet, R., Allaman, I., Pellerin, L., Magistretti, P.J., Weber, B., Comment on recent modeling studies of astrocyte-neuron metabolic interactions. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 30:12 (2010), 1982–1986, 10.1038/jcbfm.2010.132.
Mangia, S., DiNuzzo, M., Giove, F., Carruthers, A., Simpson, I.A., Vannucci, S.J., Response to “comment on recent modeling studies of astrocyte-neuron metabolic interactions”: much ado about nothing. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 31:6 (2011), 1346–1353, 10.1038/jcbfm.2011.29.
Park, J.S., Burckhardt, C.J., Lazcano, R., Solis, L.M., Isogai, T., Li, L., et al. Mechanical regulation of glycolysis via cytoskeleton architecture. Nature 578:7796 (2020), 621–626, 10.1038/s41586-020-1998-1.
Zala, D., Hinckelmann, M.-V., Yu, H., Lyra da Cunha, M.M., Liot, G., Cordelières, F.P., et al. Vesicular glycolysis provides on-board energy for fast axonal transport. Cell 152:3 (2013), 479–491, 10.1016/j.cell.2012.12.029.
Jin, M., Fuller, G.G., Han, T., Yao, Y., Alessi, A.F., Freeberg, M.A., et al. Glycolytic enzymes coalesce in G bodies under hypoxic stress. Cell Reports 20:4 (2017), 895–908, 10.1016/j.celrep.2017.06.082.
Yang, J.-S., Hsu, J.-W., Park, S.-Y., Li, J., Oldham, W.M., Beznoussenko, G.V., et al. GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis. Nature 561:7722 (2018), 263–267, 10.1038/s41586-018-0475-6.
Yang, J.-S., Hsu, J.-W., Park, S.-Y., Lee, S.Y., Li, J., Bai, M., et al. ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis. Nature Communications 10:1 (2019), 1–15, 10.1038/s41467-019-11932-0.
Tristan, C., Shahani, N., Sedlak, T.W., Sawa, A., The diverse functions of GAPDH: views from different subcellular compartments. Cellular Signalling 23:2 (2011), 317–323, 10.1016/j.cellsig.2010.08.003.
Lee, K.H., Cha, M., Lee, B.H., Neuroprotective effect of antioxidants in the brain. International Journal of Molecular Sciences, 21(19), 2020, 7152, 10.3390/ijms21197152.
Fransen, M., Revenco, I., Li, H., Costa, C.F., Lismont, C., Van Veldhoven, P.P., Peroxisomal dysfunction and oxidative stress in neurodegenerative disease: a bidirectional crosstalk. Advances in Experimental Medicine & Biology 1299 (2020), 19–30, 10.1007/978-3-030-60204-8_2.
Barber, S.C., Mead, R.J., Shaw, P.J., Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target. Biochimica Et Biophysica Acta 1762:11–12 (2006), 1051–1067, 10.1016/j.bbadis.2006.03.008.
Sorce, S., Stocker, R., Seredenina, T., Holmdahl, R., Aguzzi, A., Chiò, A., et al. NADPH oxidases as drug targets and biomarkers in neurodegenerative diseases: what is the evidence?. Free Radical Biology & Medicine 112 (2017), 387–396, 10.1016/j.freeradbiomed.2017.08.006.
Abe, K., Itoyama, Y., Sobue, G., Tsuji, S., Aoki, M., Doyu, M., et al. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration 15:7–8 (2014), 610–617, 10.3109/21678421.2014.959024.
Brennan, A.M., Suh, S.W., Won, S.J., Narasimhan, P., Kauppinen, T.M., Lee, H., et al. NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nature Neuroscience 12:7 (2009), 857–863, 10.1038/nn.2334.
Marrali, G., Casale, F., Salamone, P., Fuda, G., Caorsi, C., Amoroso, A., et al. NADPH oxidase (NOX2) activity is a modifier of survival in ALS. Journal of Neurology 261:11 (2014), 2178–2183, 10.1007/s00415-014-7470-0.
Seredenina, T., Nayernia, Z., Sorce, S., Maghzal, G.J., Filippova, A., Ling, S.-C., et al. Evaluation of NADPH oxidases as drug targets in a mouse model of familial amyotrophic lateral sclerosis. Free Radical Biology & Medicine 97 (2016), 95–108, 10.1016/j.freeradbiomed.2016.05.016.
Chiot, A., Zaïdi, S., Iltis, C., Ribon, M., Berriat, F., Schiaffino, L., et al. Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival. Nature Neuroscience 23:11 (2020), 1339–1351, 10.1038/s41593-020-00718-z.
Drechsel, D.A., Estévez, Á.G., Barbeito, L., Beckman, J.S., Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS. Neurotoxicity Research 22:4 (2012), 251–264, 10.1007/s12640-012-9322-y.
Chen, X., Zhang, X., Li, C., Guan, T., Shang, H., Cui, L., et al. S-nitrosylated protein disulfide isomerase contributes to mutant SOD1 aggregates in amyotrophic lateral sclerosis. Journal of Neurochemistry 124:1 (2013), 45–58, 10.1111/jnc.12046.
Rajasekaran, N.S., Connell, P., Christians, E.S., Yan, L.-J., Taylor, R.P., Orosz, A., et al. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130:3 (2007), 427–439, 10.1016/j.cell.2007.06.044.
Luzzatto, L., Nannelli, C., Notaro, R., Glucose-6-phosphate dehydrogenase deficiency. Hematology/Oncology Clinics of North America 30:2 (2016), 373–393, 10.1016/j.hoc.2015.11.006.
Garcia, A.A., Koperniku, A., Ferreira, J.C.B., Mochly-Rosen, D., Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives. Trends in Pharmacological Sciences 42:10 (2021), 829–844, 10.1016/j.tips.2021.07.002.
Savaki, H.E., Davidsen, L., Smith, C., Sokoloff, L., Measurement of free glucose turnover in brain. Journal of Neurochemistry 35:2 (1980), 495–502, 10.1111/j.1471-4159.1980.tb06293.x.
Veech, R.L., Harris, R.L., Veloso, D., Veech, E.H., Freeze-blowing: a new technique for the study of brain in vivo. Journal of Neurochemistry 20:1 (1973), 183–188, 10.1111/j.1471-4159.1973.tb12115.x.
Nissim, I., Horyn, O., Nissim, I., Daikhin, Y., Wehrli, S.L., Yudkoff, M., et al. Effects of a glucokinase activator on hepatic intermediary metabolism: study with 13C-isotopomer-based metabolomics. The Biochemical Journal 444:3 (2012), 537–551, 10.1042/BJ20120163.
Li, C., Nissim, I., Chen, P., Buettger, C., Najafi, H., Daikhin, Y., et al. Elimination of KATP channels in mouse islets results in elevated [U-13C]glucose metabolism, glutaminolysis, and pyruvate cycling but a decreased gamma-aminobutyric acid shunt. The Journal of Biological Chemistry 283:25 (2008), 17238–17249, 10.1074/jbc.M709235200.
Nissim, I., Horyn, O., Daikhin, Y., Chen, P., Li, C., Wehrli, S.L., et al. The molecular and metabolic influence of long term agmatine consumption. The Journal of Biological Chemistry 289:14 (2014), 9710–9729, 10.1074/jbc.M113.544726.
Weinberg, J.M., Venkatachalam, M.A., Roeser, N.F., Nissim, I., Mitochondrial dysfunction during hypoxia/reoxygenation and its correction by anaerobic metabolism of citric acid cycle intermediates. Proceedings of the National Academy of Sciences of the United States of America 97:6 (2000), 2826–2831, 10.1073/pnas.97.6.2826.
Moore, T., Le, A., Niemi, A.-K., Kwan, T., Cusmano-Ozog, K., Enns, G.M., et al. A new LC-MS/MS method for the clinical determination of reduced and oxidized glutathione from whole blood. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 929 (2013), 51–55, 10.1016/j.jchromb.2013.04.004.
Lee, W.N., Boros, L.G., Puigjaner, J., Bassilian, S., Lim, S., Cascante, M., Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1,2-13C2]glucose. The American Journal of Physiology 274:5 (1998), E843–E851, 10.1152/ajpendo.1998.274.5.E843.
van Geersdaele, L.K., Stead, M.A., Harrison, C.M., Carr, S.B., Close, H.J., Rosbrook, G.O., et al. Structural basis of high-order oligomerization of the cullin-3 adaptor SPOP. Acta Crystallographica. Section D, Biological Crystallography 69:Pt 9 (2013), 1677–1684, 10.1107/S0907444913012687.
Jang, S., Nelson, J.C., Bend, E.G., Rodríguez-Laureano, L., Tueros, F.G., Cartagenova, L., et al. Glycolytic enzymes localize to synapses under energy stress to support synaptic function. Neuron 90:2 (2016), 278–291, 10.1016/j.neuron.2016.03.011.
Li, S., Xiong, G.-J., Huang, N., Sheng, Z.-H., The cross-talk of energy sensing and mitochondrial anchoring sustains synaptic efficacy by maintaining presynaptic metabolism. Nature Metabolism 2:10 (2020), 1077–1095, 10.1038/s42255-020-00289-0.
Zhang, Y., Chen, K., Sloan, S.A., Bennett, M.L., Scholze, A.R., O'Keeffe, S., et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 34:36 (2014), 11929–11947, 10.1523/JNEUROSCI.1860-14.2014.
Johmura, Y., Yamanaka, T., Omori, S., Wang, T.-W., Sugiura, Y., Matsumoto, M., et al. Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science (New York, N.Y.) 371:6526 (2021), 265–270, 10.1126/science.abb5916.
Chin, R.M., Fu, X., Pai, M.Y., Vergnes, L., Hwang, H., Deng, G., et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature 510:7505 (2014), 397–401, 10.1038/nature13264.
Gut, P., Verdin, E., The nexus of chromatin regulation and intermediary metabolism. Nature 502:7472 (2013), 489–498, 10.1038/nature12752.
Brachmann, C.B., Davies, A., Cost, G.J., Caputo, E., Li, J., Hieter, P., et al. Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast (Chichester, England) 14:2 (1998), 115–132, 10.1002/(SICI)1097-0061(19980130)14:2<115::AID-YEA204>3.0.CO;2-132.
Chee, M.K., Haase, S.B., New and redesigned pRS plasmid shuttle vectors for genetic manipulation of Saccharomycescerevisiae. G3: Genes – Genomes – Genetics 2:5 (2012), 515–526, 10.1534/g3.111.001917.
Ito, H., Fukuda, Y., Murata, K., Kimura, A., Transformation of intact yeast cells treated with alkali cations. Journal of Bacteriology 153:1 (1983), 163–168, 10.1128/JB.153.1.163-168.1983.
Couthouis, J., Hart, M.P., Shorter, J., DeJesus-Hernandez, M., Erion, R., Oristano, R., et al. A yeast functional screen predicts new candidate ALS disease genes. Proceedings of the National Academy of Sciences of the United States of America 108:52 (2011), 20881–20890, 10.1073/pnas.1109434108.
Brenner, S., The genetics of Caenorhabditis elegans. Genetics 77:1 (1974), 71–94.
Nussbaum-Krammer, C.I., Neto, M.F., Brielmann, R.M., Pedersen, J.S., Morimoto, R.I., Investigating the spreading and toxicity of prion-like proteins using the metazoan model organism C. elegans. Journal of Visualized Experiments: Journal of Visualized Experiments(95), 2015, 52321, 10.3791/52321.
