The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
ER–mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43
Open accessAbstract
Mitochondria and the endoplasmic reticulum (ER) form tight structural associations and these facilitate a number of cellular functions. However, the mechanisms by which regions of the ER become tethered to mitochondria are not properly known. Understanding these mechanisms is not just important for comprehending fundamental physiological processes but also for understanding pathogenic processes in some disease states. In particular, disruption to ER–mitochondria associations is linked to some neurodegenerative diseases. Here we show that the ER-resident protein VAPB interacts with the mitochondrial protein tyrosine phosphatase-interacting protein-51 (PTPIP51) to regulate ER–mitochondria associations. Moreover, we demonstrate that TDP-43, a protein pathologically linked to amyotrophic lateral sclerosis and fronto-temporal dementia perturbs ER–mitochondria interactions and that this is associated with disruption to the VAPB–PTPIP51 interaction and cellular Ca 2+ homeostasis. Finally, we show that overexpression of TDP-43 leads to activation of glycogen synthase kinase-3β (GSK-3β) and that GSK-3β regulates the VAPB–PTPIP51 interaction. Our results describe a new pathogenic mechanism for TDP-43.
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Citations
Cites
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., et al. (2008) · Science · doi:10.1126/science.1154584 · Cited by 2,630
Self-citationMitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
An ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen
Kornmann, B., Currie, E., Collins, S. R., Schuldiner, M., Nunnari, J., Weissman, J. S., & Walter, P. (2009) · Science · doi:10.1126/science.1175088 · Cited by 1,275
Endoplasmic reticulum-mitochondria contacts: Function of the junction
Rowland, A. A., & Voeltz, G. K. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3440 · Cited by 1,018 · cited 4×
“Thus ER-mitochondrial Ca 2+ exchange following release from ER stores affects both cellular Ca 2+ homeostasis and mitochondrial ATP production since several mitochondrial dehyrogenase enzymes involved in ATP synthesis are Ca 2+ regulated 4,45 .”
InfluentialAn Actin-Dependent Step in Mitochondrial Fission Mediated by the ER-Associated Formin INF2
Korobova, F., Ramabhadran, V., & Higgs, H. N. (2013) · Science · doi:10.1126/science.1228360 · Cited by 817
Upregulated function of mitochondria‐associated ER membranes in Alzheimer disease
Area‐Gomez, E., del Carmen Lara Castillo, M., Tambini, M. D., Guardia‐Laguarta, C., de Groof, A. J. C., Madra, M., Ikenouchi, J., Umeda, M., Bird, T. D., Sturley, S. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.202 · Cited by 638
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
Ferraiuolo, L., Kirby, J., Grierson, A. J., Sendtner, M., & Shaw, P. J. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.152 · Cited by 615
Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels
Bartolome, F., Wu, H.-C., Burchell, V. S., Preza, E., Wray, S., Mahoney, C. J., Fox, N. C., Calvo, A., Canosa, A., Moglia, C., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.028 · Cited by 156 · cited 11×
“The importance of TDP-43 in the disease process is highlighted by the findings that mutations in the TDP-43 gene are causative for some familial forms of ALS/FTD 17 .”
InfluentialAmbegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · cited 6×
“Thus, TDP-43 activates GSK-3 β and GSK-3 β regulates the VAPB-PTPIP51 interaction.”
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Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives
Hajam, Y. A., Rani, R., Ganie, S. Y., Sheikh, T. A., Javaid, D., Qadri, S. S., Pramodh, S., Alsulimani, A., Alkhanani, M. F., Harakeh, S., et al. (2022) · Cells · doi:10.3390/cells11030552 · Cited by 915
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Metadata
- Authors
- Stoica, R., De Vos, K. J., Paillusson, S., Mueller, S., Sancho, R. M., Lau, K.-F., Vizcay-Barrena, G., Lin, W.-L., Xu, Y.-F., Lewis, J., Dickson, D. W., Petrucelli, L., Mitchell, J. C., Shaw, C. E., & Miller, C. C. J.
- Venue
- Nature Communications
- Published
- 2014-06-03
- Volume
- 5
- Issue
- 1
- Pages
- 3996-3996
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2066088939
- Cited by
- 618
- References
- 10
- FWCI
- 13.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
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