NP1 Regulates Neuronal Activity-Dependent Accumulation of BAX in Mitochondria and Mitochondrial Dynamics
Open accessAbstract
In cultured cerebellar granule neurons, low neuronal activity triggers the intrinsic program of apoptosis, which requires protein synthesis-dependent BAX translocation to mitochondria, a process that may underlie neuronal damage in neurodegeneration. However, the mechanisms that link neuronal activity with the induction of the mitochondrial program of apoptosis remain unclear. Neuronal pentraxin 1 (NP1) is a pro-apoptotic protein induced by low neuronal activity that is increased in damaged neurites in Alzheimer's disease-affected brains. Here we report that NP1 facilitates the accumulation of BAX in mitochondria and regulates mitochondrial dynamics during apoptosis in rat and mouse cerebellar granule neurons in culture. Reduction of neuronal activity increases NP1 protein levels in mitochondria and contributes to mitochondrial fragmentation in a Bax-dependent manner. In addition, NP1 is involved in mitochondrial transport in healthy neurons. These results show that NP1 is targeted to mitochondria acting upstream of BAX and uncover a novel function for NP1 in the regulation of mitochondrial dynamics and trafficking during apoptotic neurodegeneration.
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?
NPTX1 may act as a sensor of harmful stimuli, targeting affected neurons to apoptotic cell death.
“Moreover, it participates in synaptic pruning by activation of the classical complement cascade (Kovács et al. 2020) (Fig. 3a-5) and may act as a sensor of harmful stimuli, targeting affected neurons to apoptotic cell death (Clayton et al. 2012; Rahim et al. 2013).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Clayton et al. 2012
Intracellular NPTX1 impairs mitochondrial translocation into the synapses by reduction of anterograde trafficking.
“Moreover, intracellular NPTX1 impairs mitochondrial translocation into the synapses—required due to the high energy demand—by reduction of anterograde trafficking (Clayton et al. 2012) (Fig. 3b-3).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Clayton et al. 2012
Under low neuronal activity, NPTX1 contributes to neuronal death and neurodegeneration.
“Under low neuronal activity, NPTX1 contributes to neuronal death and neurodegeneration.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Clayton et al. 2012
Under low neuronal activity, NPTX1 is guided to the mitochondria, where it induces BAX-dependent apoptosis, allowing the release of pro-apoptotic factors.
“Under those circumstances, NPTX1 is guided to the mitochondria, where it induces BAX-dependent apoptosis, allowing the release of pro-apoptotic factors (Clayton et al. 2012).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Clayton et al. 2012
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
The BCL-2 protein family: opposing activities that mediate cell death
Youle, R. J., & Strasser, A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2308 · Cited by 4,704 · see citing works
Mitochondrial dynamics and apoptosis
Suen, D.-F., Norris, K. L., & Youle, R. J. (2008) · Genes & Development · doi:10.1101/gad.1658508 · Cited by 1,270 · see citing works
D'Mello, S. R., Galli, C., Ciotti, T., & Calissano, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.10989 · Cited by 892 · see citing works
Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Mitochondria at Synapses
MacAskill, A. F., Rinholm, J. E., Twelvetrees, A. E., Arancibia‐Cárcamo, I. L., Muir, J., Fransson, Å., Aspenström, P., Attwell, D., & Kittler, J. T. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.030 · Cited by 677 · see citing works
Misko, A. L., Jiang, S., Wegorzewska, I., Milbrandt, J., & Baloh, R. H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.6248-09.2010 · Cited by 643 · see citing works
Role of Bax and Bak in mitochondrial morphogenesis
Karbowski, M., Norris, K. L., Cleland, M. M., Jeong, S.-Y., & Youle, R. J. (2006) · Nature · doi:10.1038/nature05111 · Cited by 625 · see citing works
Nonionic Detergents Induce Dimerization among Members of the Bcl-2 Family
Hsu, Y., & Youle, R. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.21.13829 · Cited by 591 · see citing works
Axonal mitochondrial transport and potential are correlated
Miller, K. E., & Sheetz, M. P. (2004) · Journal of Cell Science · doi:10.1242/jcs.01130 · Cited by 512 · see citing works
Hsu, Y., & Youle, R. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.17.10777 · Cited by 504 · see citing works
Induction of BIM, a Proapoptotic BH3-Only BCL-2 Family Member, Is Critical for Neuronal Apoptosis
Putcha, G. V., Moulder, K. L., Golden, J. P., Bouillet, P., Adams, J. A., Strasser, A., & Johnson, E. M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00238-0 · Cited by 448 · see citing works
Mitochondrial membrane permeabilization in neuronal injury
Galluzzi, L., Blomgren, K., & Kroemer, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2665 · Cited by 418 · see citing works
Miller, T. M., Moulder, K. L., Knudson, C. M., Creedon, D. J., Deshmukh, M., Korsmeyer, S. J., & Johnson, E. M. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.1.205 · Cited by 383 · see citing works
Tsui, C., Copeland, N., Gilbert, D., Jenkins, N., Barnes, C., & Worley, P. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-08-02463.1996 · Cited by 315 · see citing works
Putcha, G. V., Deshmukh, M., & Johnson, E. M. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-17-07476.1999 · Cited by 310 · see citing works
Bax- or Bak-Induced Mitochondrial Fission Can Be Uncoupled from Cytochrome c Release
Sheridan, C., Delivani, P., Cullen, S. P., & Martin, S. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.002 · Cited by 264 · see citing works
The Soluble Form of Bax Regulates Mitochondrial Fusion via MFN2 Homotypic Complexes
Hoppins, S. C., Edlich, F., Harwig, M. C., Banerjee, S., McCaffery, J. M., Youle, R. J., & Nunnari, J. M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2010.11.030 · Cited by 243 · see citing works
Bcl-xL increases mitochondrial fission, fusion, and biomass in neurons
Berman, S. B., Chen, Y., Qi, B., McCaffery, J. M., Rucker, E. B., Goebbels, S., Nave, K., Arnold, B. A., Jonas, E. A., Pineda, F. J., et al. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200809060 · Cited by 231 · see citing works
Emerging Role for Members of the Bcl-2 Family in Mitochondrial Morphogenesis
Autret, A., & Martin, S. J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.10.011 · Cited by 190 · see citing works
Neuronal pentraxin, a secreted protein with homology to acute phase proteins of the immune system
Schlimgen, A. K., Helms, J. A., Vogel, H. S., & Perin, M. S. (1995) · Neuron · doi:10.1016/0896-6273(95)90308-9 · Cited by 163 · see citing works
Bcl-2 family interaction with the mitochondrial morphogenesis machinery
Harwig, M. C., Norris, K. L., Karbowski, M., Wang, C., Suen, D., Jiao, S., George, N. M., Luo, X., Li, Z., & Youle, R. J. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.89 · Cited by 106 · see citing works
Abad, M. A., Enguita, M., DeGregorio-Rocasolano, N., Ferrer, I., & Trullas, R. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0575-06.2006 · Cited by 102 · see citing works
Self-citationMitochondrial trafficking and morphology in neuronal injury
Rintoul, G. L., & Reynolds, I. J. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.09.005 · Cited by 68 · see citing works
McGinnis, K., Gnegy, M. E., & Wang, K. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721899.x · Cited by 60 · see citing works
DeGregorio-Rocasolano, N., Gasull, T., & Trullas, R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007967200 · Cited by 56 · see citing works
Enguita, M., DeGregorio‐Rocasolano, N., Abad, A., & Trullás, R. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.007062 · Cited by 50 · see citing works
Self-citationTseng, L. A., & Bixby, J. L. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2011.04.005 · Cited by 29 · see citing works
Loucks, F. A., Schroeder, E. K., Zommer, A. E., Hilger, S., Kelsey, N. A., Bouchard, R. J., Blackstone, C. D., Brewster, J. L., & Linseman, D. A. (2008) · Brain Research · doi:10.1016/j.brainres.2008.10.081 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Schatz, F., Guzeloglu‐Kayisli, O., Arlıer, S., Kayisli, U. A., & Lockwood, C. J. (2016) · Human Reproduction Update · doi:10.1093/humupd/dmw004 · Cited by 238 · see citing works
Gómez de San José, N., Massa, F., Halbgebauer, S., Oeckl, P., Steinacker, P., & Otto, M. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-021-02411-2 · Cited by 112 · see citing works
Unique signatures of stress-induced senescent human astrocytes
Simmnacher, K., Krach, F., Schneider, Y., Alecu, J. E., Mautner, L., Klein, P., Roybon, L., Prots, I., Xiang, W., & Winner, B. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113466 · Cited by 63 · see citing works
Urban air particulate matter induces mitochondrial dysfunction in human olfactory mucosal cells
Chew, S., Lampinen, R., Saveleva, L., Korhonen, P., Mikhailov, N., Grubman, A., Polo, J. M., Wilson, T., Komppula, M., Rönkkö, T. J., et al. (2020) · Particle and Fibre Toxicology · doi:10.1186/s12989-020-00352-4 · Cited by 60 · see citing works
Neuronal Pentraxin 1 Negatively Regulates Excitatory Synapse Density and Synaptic Plasticity
Figueiro-Silva, J., Gruart, A., Clayton, K. B., Podlesniy, P., Abad, M. A., Gasull, X., Delgado-García, J. M., & Trullas, R. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2548-14.2015 · Cited by 53 · see citing works
Self-citationKovács, R. Á., Vadászi, H., Bulyáki, É., Török, G., Tóth, V., Mátyás, D., Kun, J., Hunyadi-Gulyás, É., Fedor, F. Z., Csincsi, Á., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.599771 · Cited by 43 · see citing works
Cummings, D. M., Benway, T. A., Ho, H., Tedoldi, A., Freitas, M. M. F., Shahab, L., Murray, C. E., Richard-Loendt, A., Brandner, S., Lashley, T., et al. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx046 · Cited by 43 · see citing works
Critical role of neuronal pentraxin 1 in mitochondria-mediated hypoxic–ischemic neuronal injury
Rahim, M. A., Thatipamula, S., & Hossain, M. A. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.10.003 · Cited by 37 · see citing works
Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease
Ma, Q., Teng, E., Zuo, X., Jones, M. R., Teter, B., Zhao, E. Y., Zhu, C., Bilousova, T. V., Gylys, K. H., Apostolova, L. G., et al. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.02.014 · Cited by 32 · see citing works
Jarmalavičiūtė, A., Tunaitis, V., Strainienė, E., Aldonytė, R., Ramanavičius, A., Venalis, A., Magnusson, K., & Pivoriūnas, A. (2013) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-0046-0 · Cited by 29 · see citing works
NPTX1 mutations trigger endoplasmic reticulum stress and cause autosomal dominant cerebellar ataxia
Coutelier, M., Jacoupy, M., Janer, A., Renaud, F., Auger, N., Saripella, G. V., Ancien, F., Pucci, F., Rooman, M. J., Gilis, D., et al. (2021) · Brain · doi:10.1093/brain/awab407 · Cited by 29 · see citing works
Histone deacetylase-3: Friend and foe of the brain
D’Mello, S. R. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220928278 · Cited by 26 · see citing works
Thatipamula, S., Rahim, M. A., Zhang, J., & Hossain, M. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.12.016 · Cited by 20 · see citing works
Laparra, I. C., Juárez‐Escoto, E., Vicario‐Abejón, C., Moratalla, R., & García‐Sanz, P. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1087072 · Cited by 17 · see citing works
Neuronal pentraxin 1 depletion delays neurodegeneration and extends life in Sandhoff disease mice
Hooper, A. W. M., Alamilla, J., Venier, R. E., Gillespie, D. C., & Igdoura, S. A. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw422 · Cited by 11 · see citing works
Lim, B., Fowler, C., Li, Q.-X., Rowe, C., Dhiman, K., Gupta, V. B., Masters, C. L., Doecke, J. D., Martins, R. N., Collins, S., et al. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135078 · Cited by 10 · see citing works
Arias, C. C. W. P., Silbern, I., Gomes, L. C., Wartmann, H., Dambeck, V., Fanz, J., Neuenroth, L., Bähr, M., Outeiro, T. F., Bonn, S., et al. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15924 · Cited by 9 · see citing works
Zapata, A. G., Pontis, S., Schepers, R. J., Wang, R., Oh, E. J., Stein, A., Bäckman, C. M., Worley, P. F., Enguita, M., Abad, M. A., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2730-12.2012 · Cited by 9 · see citing works
Self-citationTryptophan Metabolites Regulate Neuropentraxin 1 Expression in Endothelial Cells
Vial, R., Poitevin, S., McKay, N., Burtey, S., & Cérini, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042369 · Cited by 9 · see citing works
Rahim, M. A., Thatipamula, S., Pasinetti, G. M., & Hossain, M. A. (2021) · ASN NEURO · doi:10.1177/17590914211012888 · Cited by 6 · see citing works
Yang, Y., Wang, Y., Wang, Y., & Ke, T. (2023) · International Journal of Neuroscience · doi:10.1080/00207454.2023.2292956 · Cited by 5 · see citing works
Knorr, U. B., Simonsen, A. H., Nilsson, J., Brinkmalm, A., Zetterberg, H., Blennow, K., Knudsen, M. B., Forman, J. L., Hasselbalch, S. G., & Kessing, L. V. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.05.034 · Cited by 5 · see citing works
Bi-phasic gliosis drives neuropathology in a Sandhoff disease mouse model
Hooper, A. W. M., & Igdoura, S. A. (2016) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2016.08.008 · Cited by 5 · see citing works
Nowacka-Chmielewska, M. M., Liśkiewicz, D., Liśkiewicz, A., Przybyła, M., Marczak, Ł., Wojakowska, A., Grabowska, K., Grabowski, M., Barski, J. J., & Małecki, A. (2022) · Nutrients · doi:10.3390/nu14091934 · Cited by 4 · see citing works
Ha, T.-Y., Lim, S. M., Park, H., & Chang, K. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01769-9 · Cited by 1 · see citing works
Clinical Validation of Neuronal Pentraxin Receptor as a Candidate Biomarker for Alzheimer’s Disease
Lim, B. (2020) · TSpace (University of Toronto)
Sumera, S., Amber, S., Mirza, F. J., Ali, A., & Zahid, S. (2021) · Research Square · doi:10.21203/rs.3.rs-930442/v1
Synaptic dysfunction as a major driver in Alzheimer's disease: Beyond the amyloid paradigm
Mierzwa, N., & Wężyk, M. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106858
- Authors
- Clayton, K. B., Podlesniy, P., Figueiro-Silva, J., López-Doménech, G., Benitez, L., Enguita, M., Abad, M. A., Soriano, E., & Trullas, R.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-01-25
- Volume
- 32
- Issue
- 4
- Pages
- 1453-1466
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6796267
- OpenAlex
- W1976470366
- Cited by
- 28
- References
- 27
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 5 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- Bax, mitochondrial dynamics, mitochondrial fragmentation, mitochondrial apoptosis, mitochondrial transport, cerebellar granule cells, neurodegeneration, Alzheimer's disease, mitochondrial targeting
- MeSH terms
- Pentraxins, Animals, Animals, Newborn, C-Reactive Protein, Cells, Cultured, Female, Humans, Male, Mitochondria, Nerve Tissue Proteins, Neurons, Rats, Sprague-Dawley, Mice, Knockout, bcl-2-Associated X Protein, Mice, Rats, Molecular Dynamics Simulation, Mice, 129 Strain, HEK293 Cells
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
